California first: Liver removed, reconstructed, re-implanted at UC San Diego.

The patient's liver was removed from the body, cooled, treated and returned tumor free.

A team led by Alan Hemming, M.D., transplant surgeon at UC San Diego Health System, has successfully performed the West Coast’s first ex-vivo liver resection, a radical procedure to completely remove and reconstruct a diseased liver and re-implant it without any tumors. The procedure saved the life of a 27-year-old mother whose liver had been invaded by a painful tumor that crushed the organ and entangled its blood supply.

“During a nine-hour surgery the team was able to remove the basketball-sized tumor,” said Hemming, professor and surgical director of the Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT) at UC San Diego Health System. “This is a surgery that carries a 15 to 20 percent risk of mortality. In this case, the patient would not have survived if she did not have surgery. This was the only way we could save her liver and her life.”

During the procedure, the diseased liver was detached from the body, flushed with preservation solution and cooled to a temperature of 4 degrees Celsius. This allowed Hemming to carefully remove the tumor from the liver in a bloodless field while preserving vital structures. Hemming then removed the tumor which weighed as much as the liver itself. Once the tumor was removed, the vessels were meticulously reconstructed. The liver was then successfully reimplanted.

“It was amazing to learn the tumor was so big and growing inside me,” said Clerisa Keirsey, mother of three and Oceanside resident. “I am glad Dr. Hemming was here to perform the surgery and happy to be going home to be with my children.”

Hemming specializes in all forms of liver surgery including split, living-related, and domino transplant procedures and has performed more than 700 liver transplants and 900 liver resections. He performs all aspects of hepatobiliary surgery including both open and laparoscopic liver resection for tumors, resection of the pancreas and bile duct, and portal decompressive procedures.

The Center for Hepatobiliary Disease and Abdominal Transplantation at UC San Diego Health System offers full spectrum liver care, from diagnostics and testing to novel therapies and clinical trials not found anywhere else in the United States.

The CHAT team includes: Robert Gish, M.D.; Alan Hemming, M.D.;Ajai Khanna, M.D.; Yuko Kono, M.D.; Alexander Kuo, M.D.; Rohit Loomba, M.D.; Kristin Mekeel, M.D.; Michel Mendler, M.D.; Heather Patton, M.D.; and Rene Pink, R.N.

Results may have important implications for counseling parents on organ donation.

Tippi MacKenzie, UC San Francisco

Children with a rare, life-threatening disease that is the most common cause of neonatal liver failure — biliary atresia — better tolerate liver transplants from their mothers than from their fathers, according to a UC San Francisco-led study.

In the study, researchers reviewed all pediatric liver transplants nationwide from 1996 to 2010, and compared the outcomes for patients who received liver grafts from their mothers with those for patients who received livers from their fathers.

Researchers believe the improved outcomes for children receiving a maternal liver graft may be due to higher levels of maternal cells in the patients’ livers. The presence of these cells may establish tolerance to maternal antigens — substances that induce an immune response — and therefore greater acceptance of maternal organs in these biliary atresia patients.

“This result is exciting because it supports the concept that trafficking of cells between the mother and the fetus has functional significance long after the pregnancy is over,” said senior author Tippi MacKenzie, M.D., assistant professor of pediatric surgery at UCSF and a fetal surgeon at UCSF Benioff Children’s Hospital. “This is a topic we are actively studying both in animal models and in patients who have fetal surgery. Practically speaking, this study may allow us to counsel families in which both the mother and father are willing and able to be a donor.”

The researchers found that patients with biliary atresia who received a transplanted maternal portion of liver had a failure rate of 3.7 percent, compared to the failure rate of 10.5 percent observed in recipients of paternal livers. In children who had liver transplantation for other diseases, there were no differences in the transplant outcome between maternal or paternal grafts.

The results will be published in the January issue of the American Journal of Transplantation and can be found online at  http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2011.03895.x/full.

Biliary atresia, which affects one in 10,000 newborn infants, occurs when the common bile duct between the liver and the small intestine is blocked or absent. While early surgical intervention to treat biliary atresia is critical to prevent irreversible liver damage, once the liver fails, a liver transplant is required.

“We were testing the idea that if cells from the mother travel into the fetus during pregnancy and are involved in maternal-fetal tolerance, this phenomenon may have a long-lasting effect for transplantation tolerance when the mother donates an organ to the child,” MacKenzie said.

Co-authors of the study are Amar Nijagal, M.D.; Shannon Fleck, B.S.; Nancy Hills, Ph.D.; Sandy Feng, M.D., Ph.D.; Qizhi Tang, Ph.D.; Sang-mo Kang, M.D.; and Phil Rosenthal, M.D., all of UCSF. It was funded by the Irene Perstein Award and a grant from the California Institute for Regenerative Medicine.

About UCSF Benioff Children’s Hospital
UCSF Benioff Children’s Hospital creates an environment where children and their families find compassionate care at the forefront of scientific discovery, with more than 150 experts in 50 medical specialties serving patients throughout Northern California and beyond. The hospital admits about 5,000 children each year, including 2,000 babies born in the UCSF Medical Center. For more information, visit www.ucsfbenioffchildrens.org.

19-year-old patient receives rare combination surgery.

Jennifer Golden received the first double lung-liver transplant performed at UCLA.

Jennifer Golden, a 19-year-old college student from Las Vegas, got her Christmas gift early this year — a pair of life-saving lungs and a liver at Ronald Reagan UCLA Medical Center on Dec. 4.

The rare combination surgery, thanks to the gift of one donor, also marked a milestone for the hospital’s organ transplant program: It was the first operation of its kind ever performed at UCLA.

The young woman has a genetic condition called cystic fibrosis, which causes thick, sticky mucus in her lungs that traps infection-causing bacteria. As a result, Jennifer experienced shortness of breath, excess mucus, coughing, an inability to gain weight and diabetes.

Her disease was managed by a routine of “tune-ups” to clear the mucus in her lungs with antibiotics, intravenous medications, physical therapy and other procedures. However, over the years, her lungs developed infections that became increasingly difficult to treat. To make matters more complicated, Jennifer’s liver function was also affected by the disease. By her senior year, she was so sick she could no longer attend high school.

At age 17, with her lungs and liver simultaneously deteriorating, she was told her only chance at life was organ donation.

“I felt every emotion — scared, nervous, but also happy that this could save my life,” Jennifer recalled.

A double lung-liver transplant surgery is rare. According to the most current data available from the United Network for Organ Sharing which manages the country’s organ donation system, only 44 lung-liver transplants have been performed in the United States. It is also unusual for a cystic fibrosis patient to need both lungs and a liver. More commonly, because of the way the disease progresses, the patient needs only one organ or the other.

“Because of her small size and the necessity for both the lungs and liver to be usable, she knew — as did we — that her wait might be long,” said Dr. Sue McDiarmid, professor of pediatrics and surgery, director of the pediatric liver transplant program and Jennifer’s doctor for 10 years.

Meantime, Jennifer’s entire lung and liver transplant team — including surgeons, physicians and anesthesiologists — spent a lot of time planning for her complex surgery. For example, the surgeons decided that the best approach would be for the lung transplant to be performed first.

“We also consulted with reconstructive surgeons to map out where we would make our incisions so that Jennifer’s abdominal muscles, bone and skin would not be impacted,” added Dr. Doug Farmer, professor of surgery and surgical director of the pediatric liver transplant program. “Our goal was to perform the surgery efficiently and with minimal blood loss.”

Two years later, on Saturday, Dec. 3, Jennifer got the call that a donor had been found. She and her mom quickly flew to UCLA while her dad followed behind in the family car.

Jennifer was wheeled into surgery around 4:45 a.m. on Dec. 4. The team’s intense planning paid off, and the 13-hour operation went smoothly.

When Jennifer came out of her surgery, her ability to breath was immediately improved. With the diseased lungs removed, her illness is now gone although her cystic fibrosis is not technically cured since it is part of her genes.

“We are quite optimistic that Jennifer will do well,” said Dr. Abbas Ardehali, professor of cardiothoracic surgery and surgical director of the heart and lung transplant program at UCLA. “This is our mission here at UCLA to expand the horizon of transplant patients we can serve.”

The former high school tennis team captain can now look to the future, and her plans include being with her fiancé, continuing her college studies and hitting the tennis courts again.

She also has a vital message to deliver.

“I hope that if a family out there is ever suffering with the death of loved one, they will consider the priceless gift of organ donation,” Jennifer said. “Someone did that for me, and it saved my life. My family and I cannot thank them enough.”

“Without organ donors and their families,　stories like Jennifer’s would have only tragic endings. Jennifer now breathes with ease — she is pink — her new liver is working very well, and all this because of this one donor whose life lives on in another,” said McDiarmid.

New type of therapy is based on small molecules that mimic the effects of hepcidin in mice.

Iron overload is a common condition affecting millions of people worldwide. Excess iron in the body is toxic, and deposits can cause damage to the liver, heart and other organs. Current treatments, researchers say, are not ideal and have significant side effects.

Iron in the body is regulated by a hormone called hepcidin, and a deficiency in this hormone can cause the iron overload seen in genetic disorders like hereditary hemochromatosis and Cooley’s anemia.

In the hopes of finding a treatment for iron overload, UCLA researchers have developed a new type of therapy based on small molecules that mimic the effects of hepcidin in mice. Published online Nov. 1 in the peer-reviewed Journal of Clinical Investigation, their findings could lead to new drugs to help prevent the condition.

Hepcidin works by fitting into a receptor protein known as ferroportin, which causes a change in iron flow in the body. The UCLA team systematically worked with the hormone–receptor interface to learn how the two pieces fit together and which part of hepcidin is the most important for binding to ferroportin.

“Like with jigsaw puzzle pieces, we tried to find the best fit,” said Dr. Elizabeta Nemeth, the study’s senior author and an associate professor of medicine at the David Geffen School of Medicine at UCLA.

Nemeth, co-director of the UCLA Center for Iron Disorders, noted that this is the first attempt to develop medications that mimic hepcidin. Because hepcidin contains 25 amino acids and numerous disulfide bonds, it would be expensive and difficult to reproduce the hormone as a medication.

The UCLA team zeroed in on the areas of hepcidin and ferroportin that provided the best fit to generate iron-regulating activity. Surprisingly, they found that the first third of the hepcidin molecule had an effect similar to that of the whole molecule. They then re-engineered this portion of the molecule to make it even more effective and named the resulting new molecules “minihepcidins.”

“We found that just a few amino acids were enough to provide an effective scaffold for the minihepcidin design,” said Piotr Ruchala, a visiting assistant professor of medicine at the Geffen School of Medicine.

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San Diego community forum, featuring information on upcoming trials, is set for Oct. 20.

Alexander Kuo, UC San Diego

A collaborative partnership between the UC San Diego Liver Center and Antiviral Research Center (AVRC) has resulted in 19 clinical trials for hepatitis C virus (HCV), focused on developing more effective and well-tolerated HCV treatments.

Alexander Kuo, M.D., an associate professor of medicine at UC San Diego School of Medicine and medical director of the Liver Transplant Program at the UC San Diego Liver Center, is excited about the collaboration.

“The Liver Center provides patients outstanding patient care through its Hepatitis Clinic and Transplant Program,” said Kuo, a lead researcher in the HCV clinical trials. “The AVRC brings with it the knowledge of 25 years of experience in international antiviral clinical research. Together, we can offer members of the community access to HCV treatment options they might not otherwise have, while working to understand the best treatments for the disease.”

According to the Centers for Disease Control and Prevention, approximately 5 million to 7 million Americans have HCV infections, with 20,000 new infections occurring each year. Of those living with HCV, an estimated 3 million have chronic infections and 1 million are expected to develop cirrhosis of the liver by 2020.

“Many of these patients will develop life-threatening complications of decompensated cirrhosis or liver cancer and may require liver transplantation in the next decade,” said Kuo. “By developing effective, well-tolerated treatments to cure HCV, we can halt the progression of this disease and save lives. “

David L. Wyles, M.D., an assistant professor of medicine in UC San Diego’s Division of Infectious Diseases and a researcher at the AVRC, agrees that clinical trials benefit medical research as much as it does patients.

“With the launch of our HCV clinical trials, we begin researching some of the most advanced HCV treatment regimens available,” said Wyles. “Through research come better HCV treatments and the ability to reduce complications such as cirrhosis and liver cancer. Ultimately, wide-scale implementation of effective HCV treatment may lead to decreases in HCV incidence.”

The creation of the HCV clinical trials positions UC San Diego School of Medicine to assume national leadership on HCV clinical research, while meeting the public health needs of the community.

In San Diego County, it is estimated that more than 4,000 people are infected with HCV. Those living with HCV are prime candidates to participate in clinical trials, particularly if they have never been treated or failed their previous treatments.

Those wishing to learn more about participating in HCV clinical trials can contact the HCV screening coordinator at (619) 543-8080 or attend the upcoming HCV Community Forum, hosted by the AVRC on Oct. 20 from 6 to 9 p.m. at the San Diego LGBT Community Center, 3909 Centre St., Hillcrest. The forum will offer presentations by UC San Diego faculty on HCV medications and treatments, including two new medications that received FDA approval this summer. There will also be information available regarding HCV clinical trials and educational opportunities. Individuals living with HCV and the general public are invited to attend the free forum.  A light dinner will be served for those who RSVP in advance.

To RSVP for the Hepatitis C Community Forum or get more information, visit www.hcvforum.eventbrite.com.

HCV is the most common chronic blood-borne infection in the U.S. It is transmitted primarily by direct contact with blood. An HCV infection can by diagnosed through a number of blood tests and is curable with appropriate treatment. If left untreated, HCV can lead to liver disease and cirrhosis of the liver.

UCLA researchers identify eight risk factors for potential re-transplantation failure; develop risk scoring system.

Johnny Hong, UCLA

FINDINGS:

World first performed at UC San Diego.

Robert Gish (left) and Alan Hemming, UC San Diego

For the first time ever, a surgical team led by Alan Hemming, M.D., has successfully performed a domino transplant using a liver with a rare genetic disorder called methylmalonic acidemia (MMA).

“This extraordinary procedure allowed us to use one donated liver to save two lives,” said Hemming, professor and co-director of the Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT) at UC San Diego Health System. “This procedure is technically more difficult but allows us to expand the number of patients who can benefit from this lifesaving surgery.”

The first transplant recipient, Rafael Bolanos, 28, suffered from MMA, a metabolic disease that causes a toxic build up of amino acids in the body. He faced coma and irreversible neurologic damage. The second patient, James Ogara, 62, was diagnosed with primary sclerosing cholangitis, a chronic liver disease caused by scarring of the bile ducts.

“Liver transplantation was the only solution for both patients,” said Robert Gish, M.D., chief of hepatology and CHAT co-director.  “The challenge is that donated livers are in short supply, even for patients who desperately need transplantation.”

With two transplant teams performing simultaneous surgeries, the patient with MMA, Bolanos, received a new liver from a donor. His liver was then transplanted or “dominoed” into the second patient, O’Gara. Even though O’Gara received a liver with a genetic disorder, it will not impact his health. His body will be capable of clearing the amino acids and will be symptom-free.

“I saw this as a tremendous opportunity,” said O’Gara, 61, a real estate developer from Ramona. “The doctors did not sugarcoat the risks of receiving this organ. They explained everything and even encouraged me to seek a third-party opinion. When the call came to get the liver, I said, ‘Sign me up.’”

O’Gara added, “I have had great results. I feel good and my spirits are high. They saved my life and I am deeply grateful.”

According to the U.S. Department of Health and Human Services, more than 16,170 patients await a liver transplant each year in the United States.  Approximately 15 percent of patients on the transplant list will die while waiting for an organ to become available.

Hemming specializes in split, living-related, and domino procedures and has performed more than 700 liver transplants and 900 liver resections. He performs all aspects of hepatobiliary surgery including both open and laparoscopic liver resection for tumors, resection of the pancreas and bile duct, and portal decompressive procedures.

The Center for Hepatobiliary Disease and Abdominal Transplantation at UC San Diego Health System offers full spectrum liver care, from diagnostics and testing to novel therapies and clinical trials not found anywhere else in the United States.

The CHAT team includes: Ajai Khanna, M.D.; Yuko Kono, M.D.; Alexander Kuo, M.D.; Rohit Loomba, M.D.; Kristin Mekeel, M.D.; Michel Mendler, M.D.; Heather Patton, M.D.; and Rene Pink, R.N.

Clinic will offer patients a full spectrum of liver care.

Robert Gish (left) and Alan Hemming, UC San Diego

Patients in Nevada seeking care for liver disease may now access the university-level expertise of UC San Diego Health System’s Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT). Led by Robert Gish, M.D., world-renowned hepatologist, patients may benefit by having access to a full spectrum of liver care, from diagnostics and testing to novel therapies and clinical trials not found anywhere else in the state. Located at 3033 W. Horizon Ridge Parkway, Suite 101, in the city of Henderson, patients may make appointments by calling toll free 1-855-LV LIVER (1-855-585-4837) or 1-702-331-6303.

“I am so grateful to be able to return to the Las Vegas community to practice advanced liver care and to provide local and regional tertiary care for the patients in this region,” said Gish. “Even if you have been told that your liver disease is untreatable, there is hope for you through UC San Diego Health System experts who will come here to care for you.”

Gish will be joined by Lisa Richards, N.P., and Anthony Martinez, M.D., in the Las Vegas-based liver practice, and treat and manage patients with liver disease, in conjunction with each patient’s local health care provider. Patients who need specialized consultative care for liver transplantation or the surgical care of liver cancer will be seamlessly referred to UC San Diego Health System in San Diego.

For more than two decades, Gish has lead an extensive hepatology practice specializing in the care of liver failure, transplantation, viral hepatitis and cancer. He has served more than 22,000 patients in California and Nevada treating challenging types of liver disease in diverse populations. Gish is recognized in Southeast Asia for establishing a roadmap to improve screening, treatment for, and prevention of liver disease and Hepatitis B.

Gish is a NIH-funded researcher whose work focuses on the epidemiology of liver disease, biomarkers for liver disease and multi-targeted therapies for liver cancer, such as protein kinase inhibitors, fibroblast growth factors and iRNA technologies to prevent liver graft rejection. Novel therapies also include bio-artificial liver devices (BAL) as a bridge to transplant for patients suffering from acute liver failure.

Gish received his undergraduate training in pharmaceutical sciences at the University of Kansas in Lawrence and his medical degree from the University of Kansas in Kansas City. After graduation, he completed his internship and residency in internal medicine at UC San Diego School of Medicine and a fellowship in Gastroenterology and Hepatology at UCLA in Los Angeles. He is board certified in Internal Medicine and Gastroenterology, has the advance Certificate of Added Qualification (CAQ) in Liver Transplantation, and was formerly director of liver transplant at California Pacific Medical Center (CPMC) in San Francisco.

He is a member of the American Association for the Study of the Liver, the American Gastroenterological Association, the American Society of Transplant Physicians, and the International Liver Transplant Society, among others. Gish is fluent in Spanish and Vietnamese.

Center renamed the Oppenheimer Family Center for Neurobiology of Stress.

Investigators at UCLA’s Center for Neurobiology of Stress have been studying the links between the brain and digestive system in the development and treatment of common chronic digestive disorders in adults and children.

Now, with the support of the Gerald Oppenheimer Family Foundation, the center will expand its activities to include research into brain-body interactions in other chronic medical disorders and the biology underlying mind-based therapies. In recognition of this support, the center has been renamed the Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress.

The center’s new 5,500-square-foot facility on the UCLA campus features labs and clinic areas and houses 30 faculty and staff.

Supported by $4 million in annual federal grants, the center will receive additional support from the Oppenheimer family’s 2002 gift of $9.6 million, directed to underwrite both the center and the UCLA Center for East–West Medicine. Half of the gift has been established as an endowment to meet these programs’ long-term objectives.

The endowment will help investigators at the Oppenheimer Family Center for Neurobiology of Stress explore mind-brain-body interactions in several stress-sensitive conditions, including persistent pain disorders, such as irritable bowel syndrome and interstitial cystitis; obesity; inflammatory diseases of the liver and intestine; and chronic cardiovascular disorders. It also will support studies of the biological mechanisms underlying the effectiveness of various mind-body therapies.

“Traditionally, doctors believed that the mind and the brain had very little role or impact on chronic medical disorders, including those of the digestive system,” said Dr. Emeran Mayer, the center’s director and a professor of medicine, physiology and psychiatry at the David Geffen School of Medicine at UCLA. ”This is changing as the field grows. We are very excited to be expanding our research and clinical programs through this generous funding.”

Mayer and his team are pioneers in the characterization of brain-gut interactions in chronic abdominal pain syndromes such as irritable bowel syndrome. Recent research supports the concept that irritable bowel syndrome patients, like other chronic-pain patients, have alterations in their brain structure, characterized by a remodeling of the connections among different brain regions that play a role in pain modulation.

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New treatments form part of “triple therapy” with improved outcomes for many patients.

Lorenzo Rossaro, UC Davis

Hepatitis C, the viral liver disease afflicting more than 3.2 million people nationwide, may no longer be a painfully slow death sentence for many of those infected, thanks to two newly approved drugs tested at sites around the country, including UC Davis Medical Center.

Victor Garcia is one of the California success stories. The 59-year-old Sacramento resident recently completed a clinical trial at the medical center using Victrelis (boceprevir), the drug approved in early May by the Food and Drug Administration for general use against the disease. The other drug physicians are hailing as a cure, Incivek (telaprevir), was approved by the FDA on May 23.

“It’s extended my life,” said Garcia, a father of five. “My doctor originally told me I didn’t have that long to live, so I was really fortunate to get into the study. Now it’s amazing to think that I don’t have hepatitis C at all anymore.”

Garcia, who says he doesn’t know how he contracted the disease, took part in two clinical trials at UC Davis, one of the top five enrolling sites for testing the safety and effectiveness of the two drugs against the chronic virus. Victrelis was evaluated as part of a phase 3 clinical trial involving 1,500 adult patients around the nation. A protease inhibitor that prevents viral replication, Victrelis was tested on Garcia and other hepatitis C patients who had previously been treated with other drugs, but were unable to be cured.

Victrelis, like Incivek, is part of a “triple therapy.” The drug is added to the current standard of care for hepatitis C — a combination of the drugs peginterferon alfa and ribavirin, which among Latino and African-American patients had a low success and cure rate. In Garcia’s case, the addition of Victrelis made all the difference.

“This is an exciting time,” said Lorenzo Rossaro, professor of internal medicine and chief of the Division of Gastroenterology and Hepatology at UC Davis, who directed the clinical trials at the medical center. “To realize that a majority of my patients can be cured of devastating disease is one of the most wonderful experiences imaginable for a physician.”

Rossaro co-authored recent studies published in the New England Journal of Medicine and Lancet about the impressive and sustained virologic responses hepatitis C patients had with boceprevir. He estimates that the success rates for triple therapy will be between 70 to 80 percent. The treatment, which lasts from 24 to 48 weeks, is determined by each patient’s response to the rigorous drug regimen, which consists of once-a-week injections and multiple daily pills. How well patients tolerate the drugs, and how quickly the virus is eliminated from their bloodstream, determines the length of treatment.

While the new drugs have a significantly higher cure rate, they are not 100 percent effective in all cases. Both Vitrelis and Incivek can have significant side effects — including rashes, low red-blood cell counts (anemia), nausea, fatigue, headache and diarrhea, which force one out of seven patients to halt treatment.

“Because the new hepatitis drug cocktail is so powerful, this triple therapy requires providers to closely monitor their patients,” said Rossaro. “With all the cases that now can be treated and probably cured, specialists and primary-care providers will be playing very important roles in this effort.”

Rossaro noted that using telemedicine (medical consultations using videoconferencing equipment) will be an important way to reach patients in smaller, more rural communities, as well as train more providers to help manage the disease. With an estimated 650,000 hepatitis C cases in California, he and other specialists are working with the UC Davis Center for Health and Technology to provide telemedicine consultation services, education and training for primary-care providers who can help dispense and monitor the triple-therapy drugs.

“At $1,100 a week, the new drug therapy might appear to be a very expensive,” said Rossaro. “But compared to years of clinic visits, hospitalizations, liver transplantation and the costs arising from the complications of the infection, this is extremely cost effective because it offers a complete cure. It’s going to be worth every penny.”

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Patients, caregivers and experts gather for Sacramento event targeting PSC.

Emily Spannagel was a college freshman 12 years ago when she first learned that she had a rare liver disease that could lead to liver failure and eventually require a transplant. Her illness, primary sclerosing cholangitis (PSC), results in inflammation that progressively scars and narrows the liver’s bile ducts. The disease has dictated nearly every aspect of her life since.”When I was given the diagnosis, I was in a complete state of denial,” said Spannagel, now a stay-at-home mother with an energetic 4-year-old, who has grappled with tough decisions about career and family and suffers from severe fatigue on a daily basis. “It was extremely difficult to hear that I was going to need a liver transplant in my lifetime.”

Spannagel will be among several hundred people expected to attend the seventh annual “PSC Partners Seeking a Cure” conference, which brings together patients and caregivers, and features presentations by international health experts, including Spannagel’s physician, Christopher Bowlus, an associate professor of internal medicine. The event begins on Friday, April 29, and continues through May 1 at the Sheraton Grand Hotel in Sacramento, 1230 J St., Sacramento.

Conference attendees will learn about the latest research and treatments into the incurable disease, which is estimated to affect about 6-in-100,000 people. There is no known cause for PSC, but it is thought to be related to an autoimmune disorder. Current treatments help control PSC symptoms, which include fatigue, itching and severe jaundice.

“Most patients with early PSC have no symptoms, and its presence is recognized only because of abnormally elevated blood levels of liver enzymes that often are analyzed as part of routine blood tests for physicals,” said Bowlus, who specializes in liver diseases.  “It’s a disease that is much more common among men than women, but it has equally challenging impacts on physical health.”

In addition to Bowlus, the conference includes UC Davis Health System experts Eric Gershwin, distinguished professor of medicine and the Jack and Donald Chia Professor of Medicine, Division of Rheumatology, Allergy and Clinical Immunology; John McVicar, professor of surgery and a liver transplant expert; Natalie Torok, associate clinical professor, Division of Gastroenterology and Hepatology; and Carlo Selmi, assistant professor of medicine.

PSC sufferer Spannagel has undergone a procedure to widen the strictures in the bile ducts and takes antibiotics to fight infections there. Both are temporary measures and do not stop the progression of the disease. For the Sacramento resident, the worst thing about PSC is the uncertainty of when or how the disease might develop. She noted that patients often wait with a laundry list of symptoms that show the disease’s progression, such as fevers, hypertension, esophageal varices (dilated veins), and other problems. They also must endure the wait for the day when their MELD (Model for End-stage Liver Disease) scores are high enough that they can be put on the liver transplant list.

“Being positive is key,” said Spannagel, who is looking forward to the conference and anxious to learn more about the ongoing research and any potential treatments on the horizon. “Because there are still so many unanswered questions about PSC, any new information is important. It will be truly uplifting to be in a room full of PSCers and know that we are in this fight together.”

About PCS Partners Seeking a Cure
PSC Partners Seeking a Cure is a volunteer organization formed in 2005 to provide primary sclerosing cholangitis (PSC) patients and their caregivers with education and support as well as raise funds for research into the origins of the disease and finding a cure for it.

About UC Davis Medical Center
UC Davis Medical Center is a comprehensive academic medical center where clinical practice, teaching and research converge to advance human health. Centers of excellence include the National Cancer Institute-designated UC Davis Cancer Center; the region’s only level 1 pediatric and adult trauma centers; the UC Davis MIND Institute, devoted to finding treatments and cures for neurodevelopmental disorders; and the UC Davis Children’s Hospital. The medical center serves a 33-county, 65,000-square-mile area that stretches north to the Oregon border and east to Nevada. It further extends its reach through the award-winning telemedicine program, which gives remote, medically underserved communities throughout California unprecedented access to specialty and subspecialty care. For more information, visit medicalcenter.ucdavis.edu.

UCLA researchers find that liver X receptors dampen the cirrhosis-causing actions of stellate cells.

UCLA researchers have demonstrated that a key regulator of cholesterol and fat metabolism in the liver also plays an important role in the development of liver fibrosis — the build-up of collagen scar tissue that can develop into cirrhosis. Cirrhosis, in turn, is a major cause of premature death and is incurable without a liver transplant.

Published in the March issue of the journal Gastroenterology, the study shows that liver X receptors (LXRs), master regulators of cholesterol, fat and inflammatory gene expression, also control the fibrosis-making cells of the liver, known as hepatic stellate cells.

In the face of chronic liver injury — due to excess fat, chronic viral hepatitis or alcohol abuse, for example — stellate cells become activated and launch an inflammatory and fibrotic cascade that eventually results in the build-up of collagen scar tissue in the liver.

LXRs, when stimulated, “turn on” several hundred genes that hold instructions to create proteins for carrying out bodily processes in cells, from transporting and excreting cholesterol to synthesizing fat in the liver. They have also been shown to suppress inflammatory processes in several contexts.

“Our work sets the stage for looking at new ways to modulate cholesterol and/or fat metabolism in order to have therapeutic potential for the treatment of fibrosing liver diseases,” said lead author Dr. Simon Beaven, an assistant professor of digestive diseases at the David Geffen School of Medicine at UCLA.

The research was done in the laboratory of senior author Dr. Peter Tontonoz, a professor of pathology and laboratory medicine at the Geffen School of Medicine and a Howard Hughes Medical Institute investigator.

Beaven noted that the recent rise in obesity has resulted in a surge in the prevalence of a condition known as fatty liver, which can be a precursor to fibrosis and chronic liver disease. Simple fatty liver, also known as non-alcoholic fatty liver disease, or NAFLD, is one of the most common reasons patients consult a liver doctor in the United States. Cirrhosis due to fatty liver is skyrocketing and within a decade may become the most common indication for liver transplantation.

Beaven said the need to find better treatments for liver disease is crucial.

“A ‘holy grail’ for liver researchers is to develop anti-fibrotic treatments that target activated stellate cells in order to slow or prevent the development of cirrhosis,” Beaven said. “Our study offers the first detailed look at how LXRs specifically impact the activation of hepatic stellate cells and the subsequent development of liver fibrosis in animal models.”

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