TAG: "Transplants"

Facebook connection leads to lifesaving organ transplant


‘I call James Lebowitz my angel,’ donor recipient says.

By Yadira Galindo and Jackie Carr, UC San Diego

In January 2015, the lives of more than 60 people changed forever when Paul and Susan Lebowitz made the decision to donate their son’s organs and body tissue to recipients across the United States.

That month their beloved son James had suffered a fatal brain aneurysm at his university dormitory at Cal Poly Pomona. Doctors informed the parents that James’ life could not be saved and suggested organ donation.

In shock and grief, Paul posted a message to Facebook announcing the loss of 18-year-old James, “I don’t want to say goodbye, I thought we had a whole lifetime together.”

After discussion with his wife, a second Facebook message offered the possibility of organ donation.

“If you know someone on an organ transplant list, please let me know,” posted the father. “We can potentially direct a donation from James to help them. We have a day.”

Luckily, a man named George Martinez and his longtime friends Tommy and Randy were among Facebook’s 1.3 billion registered users. The men read Paul’s post and immediately replied by tagging and suggesting George as a potential recipient. Minutes later, a connection was made.

Martinez is a 15-year Navy veteran who works as a substance abuse assessor for the San Diego County Office of the Public Defender. He counsels people with substance abuse issues to get the help they need. George’s life was split between work and undergoing continuous medical treatment for kidney failure.

For 3.5 years, Martinez sat through dialysis from 6 p.m. to 3 a.m. three days a week. He would sleep for a few hours and then go to work. George was looking at an additional 2.5 years of dialysis before his turn could come up on the transplant list.

“My family members were not a match for an organ donation,” said Martinez. “My friends that tried were not a match either. I don’t think I could have waited another 2.5 years. I felt my body was really getting weak. It was getting hard to go to work. I’m more surprised than anybody that Facebook came to my aid.”

After hearing Martinez’s story, the Lebowitzs knew that helping George would not only save his life, but it would also help hundreds of other people he counseled on how to overcome addiction and return to a healthy lifestyle.

“It hit me in an instant as we watched over our son, that someone we know, or one step away from us, might be on the transplant list,” said Paul. “For my wife and I, there was no choice to be made. My son could help others. He liked to help people feel good and to fix problems. I have no doubt that James would want to do this.”

The amount of time a patient waits on a transplant list varies by geographic location. In San Diego, the average wait is five to seven years. In 2014, there were more than 20,000 people waiting for a kidney transplant in California — but only 2,000 people received one. More than 100,000 people in the U.S. are waiting for a kidney.

“We are in desperate need for lifesaving organ transplants in the United States,” said Dr. Kristin Mekeel, surgical director of the Kidney and Pancreas Transplantation Program at UC San Diego Health System. “Right now, there are more than 120,000 people listed for organ transplants, but only 24,000 transplants are done per year. The number of patients on the transplant list grows longer every year, but the number of donors remains static. The only way we can make up the difference is having more donations.”

George underwent a successful kidney transplant surgery at UC San Diego Medical Center, the largest kidney transplant program south of Los Angeles.

“Wow — UC San Diego — what a team. For the first three days after the surgery, I thought I was the only patient in the hospital. I don’t think I went five seconds that I pressed a button that a nurse was not there,” said Martinez. “The team kept me informed of everything.”

Martinez’s health has improved each day, allowing him to participate in a paddle out memorial service at La Jolla Shores to honor James and his lifesaving gift. Dozens of people on kayaks, boards and a boat joined the Levowitzs to say thank you and goodbye to a young man who helped more people than he’ll ever know.

“My commitment to the Lebowitz family is to get well, take care of this kidney and continue to help people,” said Martinez. “I want to help continue James’ legacy of caring.”

James saved Martinez and four additional people who were matched through the organ donation waiting list. A 50-year-old California man received James’ second kidney while a 60-year-old Californian was given his liver. A Nebraska man in his 30s was gifted James’ lungs and, fittingly, an 18-year-old Californian received his heart.

“Not only are you helping individuals, but each one of these people that James saved has a family and friends,” said Paul. “We’re really talking about touching a thousand people or more. You should register to be an organ donor.”

Tissue banks have a very limited supply of donated skin, bone, heart valves, tendons and corneas­— making James a hero to many people. Tissues from his corneas have helped two people see again.

“I call James Lebowitz my angel,” said Martinez. “I cannot imagine what they went through to make the decision to help others through their loss. I would encourage people to please be organ donors. An act of kindness and love can go so far.”

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New tool predicts whether liver cancer will recur in transplant patients


UCLA researchers develop method to more accurately calculate risk of disease recurring.

Ronal Busuttil, UCLA

By Kim Irwin, UCLA

UCLA transplant researchers have developed a novel method to more accurately calculate the risk of disease recurring in people with liver cancer who have undergone a liver transplant. The approach gives physicians a new tool to help make treatment and surveillance decisions.

The study, led by Dr. Ronald Busuttil, the William P. Longmire, Jr. Chair in Surgery and director of the Pfleger Liver Institute and Dumont–UCLA Transplant and Liver Cancer Centers, was published by the peer-reviewed Journal of the American College of Surgeons.

The research team developed a predictive calculator called a nomogram after analyzing 30 years’ worth of data from liver transplants for people with liver cancer. The study drew from records of 865 patients at UCLA between 1984 and 2013, said Dr. Vatche Agopian, an assistant professor of surgery in UCLA’s division of liver transplantation and the study’s first author.

Prior to 1996, there were no criteria to guide which liver cancer patients might be good candidates for transplants. Patients with tumors of all sizes and numbers underwent transplants, and many of them suffered early recurrence of the disease. In 1996, guidelines known as the “Milan criteria” were introduced, recommending that transplants be limited to patients who had a single tumor measuring 5 centimeters or less and those who had up to three tumors, as long as no single tumor was larger than 3 centimeters.

Agopian said one shortcoming of the Milan criteria was that they didn’t take into account the aggressiveness of the tumor or other blood biomarkers that can help predict recurrence. UCLA’s nomogram uses three groups of factors to predict recurrence more accurately than the Milan criteria and the existing American Joint Committee on Cancer pathologic TNM staging system, giving transplant physicians and oncologists more information to help decide how often to monitor patients for recurrence and whether or not adjuvant treatment is necessary.

“This novel nomogram includes three important groups of information that proved to be very accurate in predicting recurrence in liver cancer patients — better than any other system out there,” Agopian said. “Physicians can use our nomogram and have a meaningful discussion with transplant recipients regarding their post-transplant risk of cancer recurrence. It can help them decide how closely to follow their patient — a patient with a low risk of recurrence may not need screening as often — or whether a patient with a high risk of recurrence might need treatment following the transplant.”

The three groups of factors that comprise the UCLA nomogram are:

  • Pre-transplant radiologic information, or the number and size of tumors on MRI and CT scans
  • Three pre-transplant blood biomarkers thought to be predictive for cancer recurrence
  • Pathological characteristics of the explanted liver. (The diseased liver is studied to determine the aggressiveness of the tumor and whether the cancer has invaded the liver’s blood vessels, factors that can’t be determined before transplant.)

Under the Milan criteria, for example, a patient with a 5 centimeter tumor might have qualified for a liver transplant, but the UCLA-developed criteria might discover that the tumor was very aggressive and likely to recur after transplant. The nomogram also might find that a patient with a larger tumor might have a very low grade cancer and have a lower risk for recurrence. Using specific details about each patient provides an individualized profile of predicted risks for cancer recurrence, Agopian said.

“The Milan criteria presented a major step in improving the outcomes of liver cancer patients undergoing transplant,” Agopian said. “However, there is now a growing consensus and body of evidence that these criteria are too conservative, and that incorporation of other factors may improve the ability to select for patients with favorable tumor biology, regardless of size, who stand to benefit from liver transplantation.”

About 32,000 Americans will be diagnosed with liver cancer this year. Of those, 23,000 will die of their disease. Liver cancer is the sixth most common cause of cancer worldwide, and the third most common cause of cancer-related death. In the U.S., the incidence of liver cancer has nearly doubled over the past two decades. For most patients who are diagnosed with liver cancer, the disease generally is too advanced to treat with surgery. For patients with underlying liver dysfunction who are unable to undergo surgery to remove the tumor, a liver transplant is the best way to treat the patient.

“In the largest single-institution experience with liver transplant for liver cancer, excellent long-term survival was achieved,” the study reports. “Incorporation of routine pre-transplant biomarkers to existing radiographic size criteria significantly improves the ability to predict post-transplant recurrence, and should be considered in recipient selection. A novel clinicopathologic prognostic nomogram accurately predicts liver cancer recurrence after liver transplant and may guide frequency of post-transplant surveillance and adjuvant therapy.”

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Infant leaves UCLA’s Mattel hospital for home with a transplanted heart


Drayvn is the hospital’s second youngest heart transplant recipient.

Drayvn Johnson got a heart transplant when he was 23 days after he was born with a heart defect and only one coronary artery. Now 5 weeks old, he left Mattel Children's Hospital UCLA for home today with his mother, Nicole Eggleston. (Photo by Reed Hutchinson, UCLA)

By Amy Albin, UCLA

Staff at Mattel Children’s Hospital UCLA witnessed a happy ending today (March 11) instead of what could have easily been a tragic one  when they bid farewell to 5-week-old Drayvn Johnson, who went home with his mother, Nicole Eggleston, and two older brothers after becoming the hospital’s second youngest heart transplant recipient. He was only 23 days old when he received his new heart, which was the size of a strawberry.

“All of our heart transplant patients are special, but I think this one was special because we knew there was a risk we might not find a donor in time,” said Dr. Juan Alejos, professor of pediatric cardiology and director of the Pediatric Heart Transplant Program at Mattel Children’s Hospital UCLA

Dravyn was born with a condition called pulmonary atresia in which the pulmonary valve does not form properly. It was discovered during Eggleston’s pregnancy in a sonogram performed at 22 weeks. Doctors had thought initially that his heart could be repaired with a series of corrective surgeries performed over the first few years of Dravyn’s life.

However, when he was born in early February at an Orange County hospital, doctors found that he had only one coronary artery instead of two and determined that surgery would be too risky for the baby.

At 5 days old, Drayvn was airlifted to Mattel where doctors confirmed that the only hope for his survival was an urgent heart transplant. Miraculously, within two days after Drayvn’s name went on a list for a transplant, a donor was found. And Drayvn got his new heart. The hospital’s youngest heart recipient was a 16-day-old infant who received a transplanted heart in 1994.

The UCLA Pediatric Heart and Heart-Lung Transplant Program is one of the major referral centers for the western United States. The team has performed more than 300 pediatric heart transplants since 1984 when it did its first such surgery. The program is a coordinated effort among pediatric cardiologists, cardiothoracic surgeons, dentists, nurse practitioners, transplant coordinators, nutritional specialists, social workers and child developmental specialists. For more information, visit http://transplants.ucla.edu/heart.

The family has set up a website to help raise funds for Drayvn’s care.

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Three receive kidney transplants in live donor chain at UC Irvine


For one recipient, identifying a suitable kidney ‘like finding a needle in a haystack.’

Three Orange County people have received kidney transplants at UC Irvine Medical Center thanks to the altruism of an anonymous donor.

The donation started a three-way donor chain in which two people who were not tissue-compatible with their loved ones could offer their kidneys to others who suffered from end-stage renal failure and were tissue matches.

“Three people received transplants that would not have happened without the generosity of one altruistic donor,” says Dr. Clarence Foster III, director of the UC Irvine Health Kidney Transplant Program. He said one of the recipients had medical complications that made identifying a suitable kidney “like finding a needle in a haystack.”

Foster says the donors and recipients are doing well several weeks after he and Dr. Hirohito Ichii recovered the organs and transplanted them over two days.

Designated living donors have become more common in recent years as family members or friends who are a tissue match donate organs to loved ones.  More rare are donors with no connection to someone in need of a transplant but who chooses to donate to a stranger. Such unspecified donors, as they are called in the transplant community, can spark a chain that gives the gift of life to many more people.

This month’s set of transplants is Orange County’s second matched donor chain. Last year, Foster transplanted a donated kidney into a woman who had spent eight years on dialysis while waiting for an organ to become available. Her transplant became possible when an anonymous Yorba Linda man donated a kidney that was a match for a Huntington Beach resident. That recipient’s spouse could then donate a kidney that was matched and subsequently transplanted into the long-term dialysis patient.

More than 100,000 people in the U.S. are waiting for a kidney to become available. At UC Irvine Health transplant specialists have been providing kidney transplants to patients with end-stage kidney disease for more than 40 years. A comprehensive range of transplant services is available, including living kidney donations.

For more information or to make an appointment, please call the UC Irvine Health Kidney Transplant program at (714) 456-8441.

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Blood test predicts signs of acute rejection in kidney transplants


UCSF finding could lead to earlier detection, treatment and improved organ survival.

Researchers at UC San Francisco have developed a potential test for diagnosing and predicting acute rejection in kidney transplants, a finding that eventually could replace the need for biopsies and lead to earlier detection and treatment.

The study is in today’s (Nov. 11) issue of PLOS Medicine.

“We have found a set of genes in blood that pick up inflammation and acute rejection in different solid organ transplants and thus can replace the need for an invasive biopsy in the future,” said senior author Minnie Sarwal, M.D., Ph.D., professor of transplant surgery at UCSF. “This assay also predicts the onset of histological rejection by three to four months, meaning graft inflammation can be treated early and proactively, even reversed.”

“This is the first assay of its kind that can provide a sensitive readout of very early rejection and inflammation in the organ, which cannot be picked up by any other blood test on the market,” Sarwal continued. “The result is improved graft function and survival.”

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Bonded by love and life-saving transplant


Lisa Flowers donated a kidney to give her daughter a normal adolescence.

Kaylyn Flowers experienced kidney failure at just 10 years of age, but returned to a fairly normal adolescence after an organ donation from her mother, Lisa.

Lisa Flowers knew her 10-year-old daughter Kaylyn’s fatigue wasn’t normal, but the urgent call from the local doctor still took her aback.

Physicians had been testing the girl to determine if a recent eye problem was due to an autoimmune disease, and they hadn’t given Lisa reason to think anything was seriously wrong. Now they reported that Kaylyn’s kidneys had been failing, quietly but completely, and that she would likely require a transplant.

“It’s one of those moments in your life that you’ll always remember, one of those life-changing phone calls,” Lisa said. “The doctor said, ‘She won’t die from this, and we’ll do everything that we can, but it’s really serious and we need her seen within the hour. Go pack, and I’ll call you back.’ ”

Yet thanks to her mother’s love, Kaylyn would return to a fairly normal adolescence within just five months. Testing revealed that Lisa was a match to donate a kidney to her daughter, a major undertaking but one that would spare the girl years of disruptive dialysis treatments.

UC Davis’ nationally renowned nephrology and transplant programs were available to perform the procedure a short drive from the family’s Roseville home.

“Everything fell in line perfectly for us,” Lisa said. “The transplant team responded right away when we said dialysis was not for us. They came immediately, started the workup and it couldn’t have gone any easier.”

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Potential blood test uncovered for disorder than can accelerate organ failure


Discovery could allow for customized therapies, improved patient selection for transplant.

Researchers at UC San Francisco and Rush University Medical Center, Chicago, may have found a predictor for a disorder affecting kidney transplant recipients that can accelerate organ failure, a discovery that eventually could allow for customized therapies and improved patient selection for transplant.

The study of focal segmental glomerulosclerosis (FSGS), a devastating form of kidney disease, is in today’s (Oct. 1) issue of Science Translational Medicine. Research was conducted by an international study team, with Necker Hospital in Paris and UCSF joint lead authors and Rush University Medical Center and UCSF joint senior authors.

“This is a new blood test to monitor patients before kidney transplant and predict who may have recurrence of FSGS, thereby preventing loss of kidneys,” said co-senior author Minnie Sarwal, M.D., Ph.D., professor of transplant surgery at UCSF.

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Teens help family of girl with liver cancer


Westside teens ‘aiming to do good wherever good can be done’ aid UCLA patient, her family.

David Mezquita kisses his 4-year-old daughter Vicky, who has liver cancer and is undergoing treatment at Reagan UCLA Medical Center. To help the family pay for nursing care, an organization of Westside teenagers raised money through a garage sale.

When Myra and David Mezquita of the South Bay had triplets, they knew they were blessed even though they had their hands more than full caring for the new arrivals as well as their teenagers.

Then one of the triplets, Vicky, was diagnosed with liver cancer and needed a transplant, which was performed at UCLA in April 2013 by Dr. Ronald Busuttil, distinguished professor and executive chairman of the UCLA Department of Surgery. Things seemed to be going well at first. But sadly, less than a year later, Vicky was diagnosed with recurrent cancer in her new liver.

To eradicate some liver tumors that remained unaffected by the chemotherapy, the 4-year-old underwent chemotherapy and stereotactic body radiation therapy (SBRT), a newer radiation treatment that noninvasively focuses high doses of radiation to kill tumors in a few treatment sessions.

The Mezquitas were juggling treatment appointments and caring for their other children when they lost crucial supplemental funding they had used to pay for nursing care for Vicky. Piling onto the family’s troubles, a utility-sparked fire that occurred about the time of Vicky’s transplant destroyed their backyard, including all the fencing and landscaping, leaving the children no safe place to play. Because of Vicky’s need for intense care following the transplant, no repairs were ever made, said her mother Myra Mezquita.

Members of Teamwork Makes the Dream Work join medical staff and family members at Vicky Mezquita's bedside in Reagan UCLA Medical Center.

Fortunately, some Westside teens who raise money to help sick children through a charity they co-founded, Teamwork Makes the Dream Work, found out about the family’s plight. Guided by the organization’s motto, “Aiming to do good wherever good can be done,” they held their annual garage sale and raised more than $5,100 for Vicky’s family, money that will help them augment her nursing care and create a new backyard for Vicky and her siblings to enjoy.

“We went all over the Westside, from Santa Monica to West Hollywood, gathering donations for the garage sale,” group member Nahal Shakib, 19, of Pacific Palisades said. “It was really important to us to raise a lot of money.”

Shakib and three members from Brentwood — Jasmine Shaouli, 18; Leila Aframian, 17; and Devon Shalom, 17 —  recently presented a check to David Mezquita, who was visiting his daughter while she was in Reagan UCLA Medical Center because of a low white blood cell count caused by the chemotherapy. The teens also brought gifts for Vicky’s siblings as well.

Dr. Julie Kang, a resident in the Department of Radiation Oncology, was able to connect the teens with the Mezquita family through a mutual friend. Kang was there when the check and gifts were presented to the family, along with Vicky’s radiation oncologist, Dr. Percy Lee, who oversaw the radiation treatments, and nurse Adriana Grandpre-Aguiar, who assisted with her care.

“It takes a lot of help to make good things happen,” the grateful father said. “I’m very happy and pleased that everyone joined together as a team to make this happen. I’m very touched.”

Myra Mezquita said that, at times, the circumstances her family is dealing with are “beyond imaginable. I can’t express the magnitude of our gratitude for the support we received from everyone.”

Lee, an associate professor of radiation oncology and director of UCLA’s SBRT program, said he was pleased they were able to treat all the visible cancer with the new radiation therapy. “This little girl has been through a lot in the last four years, and we are hopeful that the treatments give her a fighting chance,” he said.

Lee added that he was glad the family was getting some financial assistance. Even with their money woes, he said, the Mezquita family had recently given him a thoughtful gift card to pay for his lunch at a local eatery.

Kang said it was difficult watching the Mezquitas guide their child through a second bout of liver cancer.

“Parents can sometimes feel so alone in this big battle,” she said. “It’s beyond amazing that these angels came out of nowhere to help them out.”

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Seeing the future: Whole eye transplant under development


Could be ‘holy grail’ for vision restoration.

Jeffrey Goldberg, UC San Diego

The concept of a whole eye transplant seems futuristic, if not impossible. But with a $1 million grant from the U.S. Department of Defense, researchers at UC San Diego School of Medicine hope to someday make implantation of an entire, functional eye a reality.

“A whole eye transplant could be a holy grail for vision restoration,” said Jeffrey Goldberg, M.D., Ph.D., professor of ophthalmology and grant co-recipient with colleagues at University of Pittsburgh Medical Center and Boston Children’s Hospital/Harvard University. “It is in the realm of scientific plausibility.”

The basic idea is straightforward: Doctors would implant a donor eye in the recipient’s eye socket. The vascular system to the eye would be re-established, as would the eye’s musculature to enable normal movement. The greater challenge – and focus of the two-year project – would be devising effective methods to reconnect the eye’s neuronal wiring to the brain through the optic nerve, which contains more than 1 million nerve cells and transmits visual information from the retina.

Past experiments at University of Pittsburgh Medical Center have demonstrated the ability to perform whole eye transplants in genetically inbred rats (selected to minimize issues of tissue rejection). But while retinal tissue in the transplanted eyes appeared healthy, the optic nerves did not recover and regenerate connections, eliminating the possibility of restored sight.

“We know from previous experiments that the biggest scientific hurdle is not hooking up all the eye’s tiny blood vessels or its musculature,” said Goldberg, who is also director of research at UC San Diego Shiley Eye Center. “It’s that when you cut the optic nerve, the nerve cells do not regrow.”

“Our goal for this project is to be able to transplant a whole eye in an animal model and successfully demonstrate neuronal regrowth from the donor’s eye to the recipient’s optic nerve,” he said.

Researchers at UC San Diego and Harvard University have developed a variety of molecular techniques for enhancing optic nerve regeneration. One of the primary objectives is to assess whether these different techniques can be combined for greater therapeutic effect.

Among the most promising is restoring the embryonic ability of adult nerve cells to grow and blocking production of molecules that squelch nerve cells’ initial intrinsic regenerative properties. This loss of regenerative capacity is similar to what happens in spinal cord injuries that result in permanent paralysis.

Scientists have also identified proteins in the optic nerve known as neurotrophic factors that are involved in growth, survival and maintenance of developing neurons and have developed techniques for enhancing their signaling to nerve cells. Other “molecular tricks” will be used to try to overcome the inhibitory environment for re-growth normally found in the optic nerve.

If successful, researchers suggest whole eye transplants might restore sight in a wide range of patients who are blind due to structural or functional problems in the eye. For example, an estimated 120,000 Americans are blind due to damage to their optic nerves caused by glaucoma.  An estimated 186,855 eye injuries were incurred by deployed U.S. military personnel from 2000 to 2010, usually related to traumatic brain injury. Some of these cases might be remedied through eye transplants in the future.

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Pediatric transplant recipients, families celebrate at UCSF picnic


19th annual picnic points to growing success of organ transplants.

About 300 transplant recipients, donors and family members attended the 19th Annual Chris Mudge UCSF Pediatric Transplant Picnic on Aug. 23.

On a bright summer Saturday, dozens of children and their family members gathered at McNears Beach Park in San Rafael, listening to music, kayaking, having their faces painted, smashing piñatas, even playing with costumed Smurfs. For this group, the outlook wasn’t always this sunny.

The children are part of a special group: they’re pediatric transplant recipients from UCSF Benioff Children’s Hospital San Francisco.

The 19th Annual Chris Mudge UCSF Pediatric Transplant Picnic on Aug. 23 gave children who received transplants from UCSF and their families an opportunity to come together for support, to share knowledge and to celebrate having another chance at life. The 300 attendees included those who had received pre- and post-liver, kidney and small bowel transplants, as well as physicians, transplant surgeons, nurses and others from the UCSF Transplant Service.

“Some of my patients now are married and come to the picnic,” said Phil Rosenthal, M.D., former medical director of the pediatric liver transplant program and current director of pediatric hepatology at UCSF. “A lot of our families look forward to coming back to this picnic each year to reconnect.”

One of those returning patients was Justin Erickson of Redwood City. In 1992, he needed a liver transplant due to biliary atresia, a life-threatening condition in which the bile ducts are blocked.

Twenty-two years later, the 31-year-old city of San Carlos employee is a husband and father of a 5-month-old daughter.

“The first five years after the transplant, it was a real rough battle,” said Erickson, who has attended every picnic. “I had a lot of ups and downs, but I’m doing pretty good now. It’s amazing all the things I’ve accomplished and the goals that I’ve met after the transplant.”

In sharing his personal experience, Erickson has advice for pediatric patients and their families awaiting a transplant at UCSF.

“If you are looking to have a transplant at UCSF, hold your hopes up,” he said. “You definitely are talking to the right caregivers. Benioff Children’s Hospital San Francisco is the place to be with the cutting-edge technology and the doctors that have the know-how.”

Erickson is living proof of the growing success of organ transplants. Before, a 50-percent success rate was considered satisfactory. Now, thanks to medical advances and improved immunosuppressive drugs to combat infection and rejection, more than 90 percent of transplant patients are surviving, including children.

Founded in the 1960s, the UCSF Transplant Service is a world leader in clinical transplantation and has developed innovative techniques while producing superior outcomes. UCSF began pediatric kidney transplants in 1964 and pediatric liver transplants in 1989, making it among the oldest children’s transplant services in the country.

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New mouse model points to therapy for liver disease


UC San Diego findings could have impacts on obesity, organ transplantation.

Non-alcoholic fatty liver disease (NAFLD) is a common affliction, affecting almost 30 percent of Americans, with a significant number suffering from its most severe form, called non-alcoholic steatohepatitis or NASH, which can lead to cirrhosis and liver cancer. In recent years, NASH has become the leading cause of liver transplantation.

Development of effective new therapies for preventing or treating NASH has been stymied by limited small animal models for the disease. In a paper published online in Cancer Cell, scientists at the UC San Diego School of Medicine describe a novel mouse model that closely resembles human NASH and use it to demonstrate that interference with a key inflammatory protein inhibits both the development of NASH and its progression to liver cancer.

“These findings strongly call for clinical testing of relevant drugs in human NASH and its complications,” said senior author Michael Karin, Ph.D., Distinguished Professor of Pharmacology in UC San Diego’s Laboratory of Gene Regulation and Signal Transduction. “Our research has shown that, at least in this mouse model, chemical compounds that include already clinically approved drugs that inhibit protein aggregation can also be used to prevent NASH caused by a high-fat diet.”

The increasing prevalence of NAFLD is linked to the nation’s ongoing obesity epidemic. In the past decade, the rate of obesity has doubled in adults and tripled in children, in large part due to a common diet rich in simple carbohydrates and saturated fats. NASH is characterized by inflammation and fibrosis, which damage the liver and can lead to cirrhosis, hepatocellular carcinoma (HCC), the major form of liver cancer, and loss of function. Often, the only remedy is organ transplantation.

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Improving long-term health of kidney transplant recipients


UCSF is lead institution on $17M multicenter study to improve long-term survival.

Flavio Vicenti, UC San Francisco

UC San Francisco is the lead institution on a new seven-year, $17 million multicenter study funded by the National Institutes of Health to determine if certain immune system cells and/or a drug now used for treating rheumatoid arthritis can be effective in improving and maintaining the long-term health of kidney transplant recipients.

The goal of this study is to reduce or eliminate inflammation in kidney transplants and prevent the associated decline in function, thereby maximizing long-term organ survival. It will involve two clinical trials and research in parallel by biologists and by researchers for the mechanistic cores.

Despite advances in transplantation – reducing early acute rejection rates to less than 15 percent and improving one-year graft survival to more than 90 percent – long-term graft success rates have remained unchanged at 4 percent loss annually. A major contributor is progression of interstitial fibrosis and tubular atrophy in the kidney.

The cells that the researchers are focused on are regulatory T cells (Tregs), which are a small population of lymphocytes that suppress the activity of other immune cells. They maintain normal immune system homeostasis and safeguard against autoimmune diseases, and their immunosuppressive properties also can be harnessed to control transplant rejection.

Tregs have the potential to induce long-term donor-specific tolerance without impeding desired immune responses to pathogens and tumors in transplant patients.

The principal investigator of the study is Flavio Vincenti, M.D., UCSF professor of medicine and a kidney and pancreas transplant specialist at UCSF Medical Center. Other participating institutions are the University of Alabama at Birmingham, Emory University and Cedars-Sinai Medical Center.

“This grant allows us to work toward achieving two important advances in the transplant field,” said Vincenti. “We can introduce personalized medicine by treating patients based on molecular profiling of their kidney. We also can allow control of the response to the transplant by the patients’ own immune systems by regulatory T cells, either through infusions or pharmacologically.”

Researchers believe inflammation can be controlled in kidney transplant recipients by increasing the number or activity of Tregs, either by infusing them into the body or by blocking interleukin 6 (IL6) with the drug tocilizumab.

To do so, they will conduct two clinical trials – TASK (Treg Adaptive therapy in Subclinical inflammation in Kidney transplantation) and TRAIL (Therapy to Reduce Allograft Inflammation with IL6 inhibition).

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