Research with mice reveals possible strategy to reverse fibrosis in liver and other organs.

A photomicrograph of cirrhotic liver tissue, with extensive fibrotic scarring (stained blue).

An international team of scientists, led by researchers at the University of California, San Diego, School of Medicine, report that significant numbers of myofibroblasts – cells that produce the fibrous scarring in chronic liver injury – revert to an inactive phenotype as the liver heals. The discovery in mouse models could ultimately help lead to new human therapies for reversing fibrosis in the liver, and in other organs like the lungs and kidneys.

The work is published in the May 7 online Early Edition of the Proceedings of the National Academy of Sciences.

“The take-away message is twofold,” said David A. Brenner, M.D., vice chancellor for health sciences, dean of the UC San Diego School of Medicine and senior author of the paper. “First, we’ve shown that liver fibrosis is markedly reversible and we now better understand how it happens. Second, we can start looking for ways to direct active myofibroblasts to stop producing scar, and become inactive. We can focus on developing drugs that promote cell change and regression. It raises the bar for prospective treatment tremendously.”

Liver fibrosis is the 12th leading cause of death in the United States. It is the result of chronic liver injury caused by such agents as the hepatitis B and C viruses, alcoholic liver disease and non-alcoholic steatohepatitis. The condition is manifested by extensive scarring of liver tissue and the organ’s progressive inability to filter body toxins. Liver fibrosis precedes the development of liver cancer. Often, the only treatment for end-stage liver fibrosis is an organ transplant.

Fibrosis begins when infectious agents or excessive alcohol consumption trigger activation of hepatic stellate cells (HSCs), which normally act as quiescent storage units for nutrients like vitamin A in the liver. Once activated, these HSCs acquire characteristics of another cell type called myofibroblasts, which are characterized by their abundant production of extracellular matrix proteins such as collagen. These proteins accumulate as scar tissue, rendering the organ progressively dysfunctional.

However, if the source of the liver injury is successfully treated or eliminated, the liver can repair itself. In part, this is due to the activated HSCs undergoing apoptosis (programmed cell death) and being removed by other cells. But UC San Diego scientists say that, in tests using a mouse model, as many as half of all activated HSCs persist. They do not die, but rather revert to an inactive phenotype during fibrotic regression.

“After one month of regression, these cells have stopped producing collagen. They’ve upregulated some of the genes associated with quiescence and returned to their normal location in the liver,” said Tatiana Kisseleva, M.D., Ph.D., an assistant research scientist and first author of the study.

It’s not clear why these myofibroblasts survive. Also, scientists note the reverted myofibroblasts do not completely return to their original quiescent state. “They’re still more susceptible to repetitive injury than original quiescent HSCs,” said Kisseleva, who noted future tests will investigate whether additional reversion occurs with more time.

Kisseleva suggested the findings present another avenue for treating liver fibrosis, especially in possibly reverting fibrosis and cirrhosis, which accounts for roughly 27,000 deaths in the United States annually.

Fibrosis occurs in other organs as well, such as the kidneys and lungs, with comparable deadly effect. Recent studies indicate fibrotic reversibility in these organs as well. “Our findings are applicable to other fibrosing organs,” said Kisseleva. “Instead of killing damaged cells, we might be able to de-activate them and revert them to healthy originals.”

Co-authors of the study are Min Cong, Chunyan Jiang, Keiko Iwaisako, Brian Scott and Wolfgang Dillmann, Department of Medicine, UC San Diego; YongHan Paik, Department of Medicine,  UC San Diego and Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, South Korea; David Scholten, Department of Medicine, UC San Diego and Department of Medicine III, University Hospital Aachen, Germany; Thomas Moore-Morris and Sylvia M. Evans, Skaggs School of Pharmacy and Pharmaceutical Science, UC San Diego; Hidekazu Tsukamoto, Keck School of Medicine, University of Southern California.

Study based on analyses of 600 liver biopsies of patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease

People with nonalcoholic fatty liver disease (NALFD) who consume alcohol in modest amounts – no more than one or two servings per day – are half as likely to develop hepatitis as non-drinkers with the same condition, reports a national team of scientists led by researchers at the UC San Diego School of Medicine.

The findings are published in today’s (April 19) online issue of The Journal of Hepatology.

NALFD is the most common liver disease in the United States, affecting up to one third of American adults. It’s characterized by abnormal fat accumulation in the liver. The specific cause or causes is not known, though obesity and diabetes are risk factors. Most patients with NAFLD have few or no symptoms, but in its most progressive form, known as nonalcoholic steatohepatitis or NASH, there is a significantly heightened risk of cirrhosis, liver cancer and liver-related death.

NALFD is also a known risk factor for cardiovascular disease (CVD). Patients with NAFLD are approximately two times more likely to die from coronary heart disease than from liver disease. The study’s authors wanted to know if the well-documented heart-healthy benefits of modest alcohol consumption outweighed alcohol’s negative effects.

“We know a 50-year-old patient with NAFLD has a higher risk of CVD,” said Jeffrey Schwimmer, MD, associate professor of clinical pediatrics at UC San Diego, director of the Fatty Liver Clinic at Rady Children’s Hospital-San Diego and senior author. “Data would suggest modest alcohol consumption would be beneficial (in reducing the patient’s CVD risk) if you don’t take liver disease into account. When you do take liver disease into account, however, the usual medical recommendation is no alcohol whatsoever.”

Schwimmer and colleagues discovered that the benefits of modest alcohol consumption were compelling, at least in terms of reducing the odds of patients with NAFLD from developing more severe forms of the disease. Patients with NASH are 10 times more likely to progress to cirrhosis, the final phase of chronic liver disease. Cirrhosis is the 12th leading cause of death in the U.S., killing an estimated 27,000 Americans annually.

“Our study showed that those people with modest alcohol intake – two drinks or less daily – had half the odds of developing NASH than people who drank no alcohol,” said Schwimmer. “The reasons aren’t entirely clear. It’s known that alcohol can have beneficial effects on lipid levels, that it increases ‘good’ cholesterol, which tends to be low in NAFLD patients. Alcohol may improve insulin sensitivity, which has a role in NAFLD. And depending upon the type of alcohol, it may have anti-inflammatory effects.”

The study also found that in patients with NAFLD, modest drinkers experienced less severe liver scarring than did lifelong non-drinkers.

The study did not evaluate the effects of different types of alcohol, such as beer or spirits. Schwimmer said to do so would require a much larger study. Also, the study’s findings do not apply to children. All of the participants in the study were age 21 and older.

The current paper is based on analyses of 600 liver biopsies of patients with NAFLD by a national panel of pathologists who had no identifying clinical information about the samples. The study excluded anyone who averaged more than two alcoholic drinks per day or who reported consuming five or more drinks in a day (binge-drinking) at least once a month. All of the patients were at least 21 years of age.

Schwimmer said the findings indicate patients with liver disease should be treated individually, with nuance.

“For a patient with cirrhosis or viral hepatitis, the data says even small amounts of alcohol can be bad. But that may not be applicable to all forms of liver disease. Forty million Americans have NAFLD. Physicians need to look at their patient’s overall health, their CVD risk, their liver status, whether they’re already drinking modestly or not. They need to put all of these things into a framework to determine risk. I suspect modest alcohol consumption will be an appropriate recommendation for many patients, but clearly not all.”

Co-authors are Winston Dunn, departments of Pediatrics and Medicine, UC San Diego and Gastroenterology and Hepatology, Department of Medicine, University of Kansas Medical Center; Arun J. Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center; Elizabeth M. Brunt, John Cochran VA Medical Center, Saint Louis and Division of Gastroenterology, Saint Louis University School of Medicine; Aynur Unalp-Arida, Department of Epidemilogy, Johns Hopkins Bloomberg School of Public Health; Michael Donohue, Division of Biostatics and Bioinformatics, Department of Family and Preventive Medicine, UC San Diego; and Arthur J. McCullough, Department of Gastroenterology and Hepatology, Cleveland Clinic.

Funding for this research came, in part, from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development and the National Cancer Institute.

Winners include David Barba, Rohit Loomba, William Mobley, Howard Taras.

David Barba

Brain stimulation surgery for patients with Parkinson’s disease; promoting liver health on a national level; leading one of the nation’s top ALS clinics; and designing a law that protects the rights of students with epilepsy: these are significant reasons why four UC San Diego School of Medicine doctors were honored during the 18th annual Combined Health Agencies Health Hero Awards breakfast on March 15 at The Prado in Balboa Park.

Each year, the Combined Health Agencies’ 24 health nonprofit members each choose a person or company that works daily to improve the lives of local residents affected by chronic illness. This year, four winners who were recognized are UC San Diego physicians David Barba, M.D.; Rohit Loomba, M.D.; William Mobley, M.D., Ph.D.; and Howard Taras, M.D.

Since 2005, Barba, clinical professor of surgery in the Division of Neurological Surgery at UC San Diego Health System, has been involved with the Parkinson’s Association of San Diego. He routinely performs brain stimulation surgery on many patients with Parkinson’s disease and has demonstrated hisleadership by organizing a sold-out patient symposium securing top quality speakers in the field. Barba is currently establishing a UC San Diego system for those working on Parkinson’s research to be in direct contact with each other.

The American Liver Foundation considers Loomba, assistant professor of clinical medicine in the Division of Gastroenterology and the Division of Epidemiology in the Department of Family and Preventive Medicine, a collaborative partner as he serves on the National Board of Directors, and the non-profit local Speakers Bureau promoting prevention and care.

As Chair of the Department of Neurosciences at UC San Diego School of Medicine, Mobley garners national support from physicians and clinicians to join the UC San Diego ALS and Motor Neuron Treatment and Research Center team to raise the level of care and treatment of patients with ALS in San Diego. Through Mobley’s reputation and expertise, the ALS Clinic is quickly becoming known as a place where patients can receive the best care possible in their fight against what is commonly known as Lou Gehrig’s disease.

Taras, professor of pediatrics in the Division of Child Development and Community Health, is being recognized by the Epilepsy Foundation for his instrumental work in the passing of SB 161, a bill signed into law in 2011 that protects the rights of students with epilepsy. He has testified numerous times at California State Legislative hearings and spent hundreds of hours educating legislators and the public about the issue of emergency seizure rescue medications. Through this legislation, life-saving medication can be administered to students at school to prevent further brain damage or death.

“We are humbled by the service of these physicians and grateful to have UC San Diego Health System in our community,” said Susan Day, president of Combined Health Agencies.

This year’s event is possible by the generous support of community sponsors UC San Diego Health System, PhRMA, GlaxoSmithKline, Johnson & Johnson, BIOCOM, Rady Children’s Hospital-San Diego, Sonnenberg & Company CPAs, and The San Diego Business Journal.

Combined Health Agencies has been United Way’s health partner in the United Way/CHAD Campaign since 1974. As a federation of 24 local health charities, Combined Health Agencies is focused on improving the quality of life for individuals and families who are faced with chronic health conditions.

New treatments are coming for liver-damaging virus.

Alex Monto, UC San Francisco

Hepatitis C virus — not AIDS-causing HIV — is the leading chronic virus infection leading to death in the United States, and its victims most often are baby boomers. More than half who are infected do not know it.

Researchers from the U.S. Centers for Disease Control and Prevention (CDC) found in a study published in the Feb. 21 issue of the Annals of Internal Medicine that hepatitis C had overtaken HIV as a cause of death in the United States by 2007.

Deaths in the United States due to HIV infection have been steadily decreasing, and  dropped below 13,000 in 2007, while deaths from hepatitis C infection have been steadily increasing, first surpassing 15,000 per year in 2007.

The good news, according to UC San Francisco liver specialist Alex Monto, M.D., is that there has been progress in fighting both diseases, and the kinds of drug combination strategies that have done so much to transform HIV infection from a death sentence to a manageable disease are poised to further boost cure rates for those infected with hepatitis C.

“We know that not enough people with risk factors get tested,” Monto says. “There are a lot of people walking around with hepatitis C who don’t know it.”

Monto directs the liver clinic at the UCSF-affiliated San Francisco Veteran’s Affairs Medical Center, one of four hepatitis C centers nationally within the VA system. Like boomers, veterans are disproportionately affected by hepatitis C. The VA cares for 165,000 patients who are chronically infected with the virus.

Hepatitis C infects 3 million in the U.S.

Chronic Hepatitis C has been diagnosed in about three million people in the United States. It often causes no symptoms, and many who have been infected for years or even decades may remain unaware of it until symptoms finally appear. The ultimate cause of death attributable to chronic infection is cirrhosis or liver cancer, although the disease progresses to cirrhosis in fewer than half of cases. There is no vaccine.

“The main risk factor in the United States is past injection-drug use,” Monto says. “The others most at risk are those who received blood transfusions before 1992,” Monto says, referring to the year when high-quality screening of the blood supply was implemented.

[Related: Hear Alex Monto talk about hepatitis C]

Compared to HIV or hepatitis B, the risk of hepatitis C being transmitted by sex is low, Monto says, but among men who have sex with men there has been an increase in reports of the virus being sexually transmitted, more so among those who are infected with HIV.

“Anybody with a history of ever being exposed to injection drugs or who received a transfusion before the blood supply was screened should be tested,” Monto says. “That’s not controversial at all. What has been controversial is whether or not all baby boomers should be screened.”

Another study in this week’s edition of the journal suggests that a one-time blood test ordered by primary care providers to screen for antibodies to hepatitis C in those born between 1945 and 1965 would be cost effective — costing $2,874 for each chronically infected patient identified — and would lead to the identification of more than 800,000 previously undiagnosed cases.

Those who are chronically infected may be able to reduce the likelihood of disease progression by avoiding alcohol, by maintaining a healthy weight, and by being vaccinated against hepatitis A and hepatitis B, Monto says.

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UCLA discovery has implications for engineering tissues, organs.

Diagonal pattern formed by migrating cells

What if we could engineer a liver or kidney from a patient’s own stem cells? How about helping regenerate tissue damaged by diseases such as osteoporosis and arthritis? A new UCLA study bring scientists a little closer to these possibilities by providing a better understanding how tissue is formed and organized in the body.

A UCLA research team discovered that migrating cells prefer to turn right when encountering changes in their environment. The researchers were then able to translate what was happening in the cells to recreate this left–right asymmetry on a tissue level. Such asymmetry is important in creating differences between the right and left sides of structures like the brain and the hand.

The research, a collaboration between the David Geffen School of Medicine at UCLA and the Center for Cell Control at UCLA’s Henry Samueli School of Engineering and Applied Science, appears in today’s (Feb. 17) issue of the journal Circulation Research.

“Our findings suggest a mechanism and design principle for the engineering of tissue,” said senior author Dr. Linda L. Demer, a professor of medicine, physiology and bioengineering and executive vice chair of the department of medicine at the Geffen School of Medicine. “Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific left–right asymmetry, which is an important foundation in tissue and organ creation.”

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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.