TAG: "Liver disease"

Gene found that turns carbs into fat


UC Berkeley discovery could provide new target for treatments.

Fatty liver tissue

Image courtesy of The Sul Lab

A gene that helps the body convert that big plate of holiday cookies you just polished off into fat could provide a new target for potential treatments for fatty liver disease, diabetes and obesity.

Researchers at the University of California, Berkeley, are unlocking the molecular mechanisms of how our body converts dietary carbohydrates into fat, and as part of that research, they found that a gene with the catchy name BAF60c contributes to fatty liver, or steatosis.

In the study, to be published online Dec. 6 in the journal Molecular Cell, the researchers found that mice that have had the BAF60c gene disabled did not convert carbohydrates to fat, despite eating a high-carb diet.

“This work brings us one step forward in understanding fatty liver disease resulting from an excessive consumption of carbohydrates,” said the study’s senior author, Hei Sook Sul, professor at UC Berkeley’s Department of Nutritional Science and Toxicology. “The discovery of this role of BAF60c may eventually lead to the development of treatment for millions of Americans with fatty liver and other related diseases.”

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Most liver transplant candidates receive donation offers


UCSF study finds transplant wait-list deaths are not just due to organ availability.

Jennifer Lai, UC San Francisco

Most liver transplant candidates who died or were removed from the transplant list actually received one or more liver donation offers, according to a recent UC San Francisco study.

“What we found challenges the simplistic view that transplant dynamics are driven simply by organ availability,” said lead author, Jennifer Lai, M.D., assistant clinical professor in the UCSF Division of Gastroenterology and Hepatology. “Efforts to reduce wait-list mortality must target all aspects of mismatch between supply and demand.” 

Recognized as a world leader in organ transplantation since 1964, the UCSF Organ Transplant Service has performed transplants for more than 10,000 patients and has played a key role in defining the field. The UCSF Liver Transplant Program, designated as a “Center of Excellence” by the U.S. Department of Health and Human Services, performs more liver transplants than any other hospital in Northern California – over 2,300 liver transplants for adults and children since it began in 1988.

For this study, the research team analyzed data from 33,389 candidates listed in the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) registry during the time frame of Feb. 1, 2005, to Jan. 31, 2010. Out of the candidates who had died or been delisted, 84 percent received one or more liver offers prior to death/delisting, indicating that they had an opportunity to undergo transplantation. Reasons for liver offer refusals were reported as donor quality/age or other donor-related factors, size compatibility or recipient readiness.

“Understanding the real-time factors involved in the decisions regarding liver transplant offers is vital to improving the wait-list process,” said senior author, John Roberts, M.D., professor of surgery and chief of the UCSF Division of Transplantation. “While some of the factors are beyond control, others can be managed.”

Simply increasing the availability of deceased donor livers or the number of offers may not necessarily reduce wait-list mortality, according to the study, published in the leading journal in its field, Gastroenterology. Instead, the study suggests that efforts must be made to understand multiple factors involving candidates, donors and transplant centers to help influence what is often a complex and dynamic decision to accept or decline a liver offer.

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New drug successfully halts fibrosis in animal model of liver disease


Study suggests a NOX inhibitor could provide effective treatment for the disease.

David Brenner, UC San Diego

A study published in the online journal Hepatology reports a potential new NADPH oxidase (NOX) inhibitor therapy for liver fibrosis, a scarring process associated with chronic liver disease that can lead to loss of liver function.

“While numerous studies have now demonstrated that advanced liver fibrosis in patients and in experimental rodent models is reversible, there is currently no effective therapy for patients,” said principal investigator David A. Brenner, M.D.,  vice chancellor for Health Sciences and dean of the School of Medicine at the University of California, San Diego. “This new study provides important validation of the role of NOX in liver fibrosis, and suggests that a NOX inhibitor could provide an effective treatment for this devastating disease.”

Most chronic liver diseases are associated with progressive fibrosis, which is triggered by the loss of liver cells and the activation of inadequate wound healing pathways. In addition, oxidative stress — which results from an inappropriate balance between the production and clearance of highly reactive molecules involved in cell signaling called reactive oxidative species (ROS) — leads to aberrant tissue repair in the liver.

When the liver is injured — for example, through hepatitis or alcohol abuse — HSCs are activated to become myofibroblasts, cells which play a crucial role in wound healing and the body’s response to inflammation by recruiting immune cells called macrophages to the injury site. This process, triggered by intracellular signalling pathways involving NOX, can result in an abundance of scarring and eventually result in the loss of organ function.

By inhibiting NOX, the researchers theorized that myofibroblast activation and macrophage recruitment could be interrupted, preventing further fibrosis and potentially allowing regression of established fibrosis.

They assessed the effectiveness of treatment with GKT137831 — a NOX1/4 inhibitor developed by Genkyotex SA of Geneva, Switzerland — in mouse models, and found that treatment with this NOX inhibitor suppressed ROS production, as well as NOX and fibrotic gene expression.

“These data highlight the excellent pharmacological properties of GKT137831 and the broad potential for its use in fibrotic diseases,” said Patrick Page, chief development officer at Genkyotex and contributor to the study.

According to Brenner, the next steps include a clinical trial with this drug in patients with liver fibrosis.

Additional contributors include Tomonori Aoyama, UC San Diego and Juntendo University School of Medicine, Tokyo; Yong-Han Paik, Yonsei University College of Medicine, Seoul, Korea; Sumio Watanabe, Juntendo University; Benoît Laleu, Francesca Gaggini, Laetitia Fioraso-Cartier, Sophie Molangpo, Freddy Heitz, Cédric Merlot and Cédric Szyndralewiez, GenKyoTex SA, Geneva.

The study was funded in part by grants 1 R24 DK090962, 5 P50 AA011999 and 5 R01 GM041804 from the National Institutes of Health and by the American Liver Foundation.

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Deadly liver cancer may be triggered by cells changing identity


UCSF researchers triggered cellular transformation — and caused tumors to form in mice — by activating just two genes.

Holger Willenbring, UC San Francisco

A rare type of cancer thought to derive from cells in the bile ducts of the liver may actually develop when one type of liver cell morphs into a totally different type, a process scientists used to consider all but impossible. UC San Francisco researchers triggered this kind of cellular transformation — and caused tumors to form in mice — by activating just two genes. Their discovery suggests that drugs that are able to target those genes may provide a way to treat the deadly cancer, known as cholangiocarcinoma. It also shows, yet again, how the process of scientific discovery involves serendipity as well as skill.

The study appears as an advanced online publication today (July 16) in the Journal of Clinical Investigation and will appear later in the August print edition.

The two cell types, hepatocytes and biliary cells, exist side by side in the liver, but don’t normally change their “stripes” — their cellular function — let alone turn into each other. Scientists have therefore assumed that hepatocellular carcinomas, the most common kind of liver cancer, start in the hepatocytes and that cholangiocarcinomas, the bile duct cancers, start in the biliary cells.

Hepatocytes, which form the bulk of the liver, “are very good at making other hepatocytes,” said Holger Willenbring, Ph.D., an associate professor of surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and a senior author of the study. “They can divide many times but are restricted in the progeny they produce. They either produce more hepatocytes or, if something goes wrong, can cause hepatocellular carcinomas.”

The study started when Xin Chen, Ph.D., an assistant professor of bioengineering and therapeutic sciences and a senior author of the manuscript, tried to make something go wrong in the hepatocytes as a way to explore the origins of hepatocellular carcinoma. Chen and her group hoped to induce the cancer in mice by activating oncogenes, genes that trigger cancer.

Things did go awry in the hepatocytes — but not in the way the researchers expected. In specific conditions, mice developed cholangiocarcinoma instead of hepatocellular carcinoma. “We were very surprised,” Chen recalls. “How did that happen?”

The two scientists figured some of the genes they had activated might have reprogrammed the hepatocytes in a way that turned them into aberrant biliary cells, capable of forming tumors. Their chief suspects were two genes, NOTCH, which is known to be involved in the embryonic development of bile ducts, and AKT, which has been shown to play a role in many tumors.

The scientists used bits of bacterial DNA called plasmids as delivery vehicles to boost levels of NOTCH and AKT in the liver. Three-and-a-half weeks after injecting these plasmids into mice, small white growths appeared on the surface of their livers and, by five weeks, the tumors had spread through the liver. Now the scientists needed to trace the origins of these cancer cells.

Willenbring’s lab had previously developed a method for labeling mouse hepatocytes so that they, and any cell they turned into, would glow. They put this “hepatocyte fate-tracing” system to work and were able to show that the cancerous cells that formed bile duct tumors had in fact started out as hepatocytes.

For many years, scientists had believed that development of cells proceeded in one direction, moving step-by-step from primordial stem cells to fully differentiated adult cells. In recent years, researchers have shown that, by turning on certain genes, mature cells can go back in time to become stem cells or even move sideways to become other kinds of adult cell.

“This highlights how readily one cell can be converted into another and how cancer can do it for you very efficiently,” Willenbring said. “For us, it’s fairly shocking. It only took two oncogenes and it all happened in a few weeks.”

The findings also help explain another puzzle: why the incidence of bile duct cancer is higher in people with hepatitis. “Since hepatitis doesn’t do anything to biliary cells that didn’t quite make sense,” Willenbring said

Now there’s a new way to look at it, he suggests. As hepatocytes and their genomes become disarrayed by disease, Willenbring says, they may activate oncogenes in much the same way their experiment did, causing the cells to change identity and become cancerous.

Having shown that NOTCH and AKT are the triggers in this tumor-inducing process, Chen and her team are now hunting for therapies. Working with colleagues from Genentech Inc., they are testing antibodies that may blunt the activity of the genes and halt or reverse the growth of bile duct cancers in mice. “The preliminary results with the therapeutic antibodies are very encouraging,” Chen says. If they find the right formula, they may have an answer for a currently untreatable cancer.

Biao Fan, Yann Malato, Diego F. Calvisi, Syed Naqvi, Nataliya Razumilava, Silvia Ribback, Gregory J. Gores, Frank Dombrowski and Matthias Evert contributed to the research.

Funding support came from the California Institute of Regenerative Medicine, National Institutes of Health, Deutsche Forschungsgemeinschaft and the China Scholarship Council.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For further information, please visit www.ucsf.edu.

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Liver disease expert joins UC Davis faculty


Yu-Jui Yvonne Wan will serve as professor and vice chair of research.

Yu-Jui Yvonne Wan

Yu-Jui Yvonne Wan, a national leader in the study of liver diseases whose work focuses on the role of retinoids and their receptors in control of liver function, joined the Department of Pathology and Laboratory Medicine at UC Davis as professor and vice chair of research on July 1.

Wan also will serve as scientific director of a new biorepository program, working with Senior Associate Dean for Research Lars Berglund to develop a master plan to expand and unite current biorepositories into a comprehensive tissue-banking service spanning the health system. She also will participate in the Human Anatomical Specimen and Tissue Oversight Committee chaired by Executive Associate Dean Fred Meyers and will report to Department of Pathology and Laboratory Medicine Chair Lydia Pleotis Howell.

“Dr. Wan is an award-winning researcher and mentor with more than 30 years’ experience in academic medicine,” Howell said. “Her work on retinoic acid, vitamin A and related nuclear receptors is advancing knowledge of liver cell differentiation, proliferation, metabolism and disease processes, including cancer, metabolic syndrome, obesity, alcoholic liver disease and cardiovascular disease. In addition, her emphasis on translational research and education complements existing efforts under way in our stem cell biology, cancer and pharmacogenomics programs. The department and I are excited to have Dr. Wan lead integration of our clinical and research faculty into multidisciplinary collaborations that will create innovative solutions to scientific and health care problems.”

Wan came from the University of Kansas Medical Center, where she was a professor of pharmacology, toxicology and therapeutics, program leader of the Cancer Biology Program and director of the Liver Center. Before that, she was a professor of pathology at UCLA. She is recognized for establishing the Human Liver Depository, which has become an indispensible resource for scientists worldwide seeking liver tissue, serum and blood for studies. The repository contains more than 1,500 liver specimens with extensive corresponding patient data.

Wan has received many honors and awards, including the 2010 Chancellor’s Club Research Award from the University of Kansas, SIG Elsevier Mentoring Award from the Society of Toxicology, California’s Distinguished Women in Research Award and Richard Weitzman Award. She received her doctorate in pathology from Hahnemann University (now Drexel University College of Medicine) and began her career in the pathology department at UCLA.

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Hepatitis: UCSF & San Francisco at ground zero


UCSF with several initiatives to address potentially life-threatening condition.

Viral hepatitis chronically infects between 3.5 and 5.2 million people in the U.S. and more than 30,000 in San Francisco, alone — but only about 1 in 3 people who are infected know it, according to a report by the U.S. Department of Health and Human Services.

San Francisco is a clinical hot spot for viral hepatitis infection, and UCSF is at the forefront in research, public health programs, and clinical trials to prevent and fight the potentially life-threatening condition.

UCSF faculty and staff in the schools of dentistry, medicine, nursing and pharmacy and UCSF Medical Center are engaged in a range of efforts, sometimes joined by students, often with partners in San Francisco city and county government and in affected populations. They aim to educate individuals at risk for the disease about prevention and vaccination, to identify people who are infected and to ensure that those who need treatment receive it.

Among the UCSF initiatives are:

  • a free screening clinic in Chinatown
  • the use of a new computerized check-in system in UCSF Medical Center’s acute care clinic that screens for individuals at risk for hepatitis B and expedites follow-up care
  • public health awareness programs aimed at highly affected populations, including Vietnamese Americans, who have a 1-in-7 incidence of hepatitis B
  • screening and prevention outreach for injection drug users at high risk for hepatitis C infection
  • participation in the coordination and improvement of citywide activities, such as the San Francisco Hep B Free program
  • testing new treatments
  • investigating the causes of chronic infection and why vulnerability to chronic infection and treatment responses vary among individuals.

Viral hepatitis primarily is caused by three unrelated viruses — hepatitis A, B and C viruses. All attack the liver, but hepatitis B and hepatitis C are largely responsible for an increasing number of liver cancer deaths. There are effective vaccines for hepatitis A and hepatitis B, but not for hepatitis C.

Potential exposures to hepatitis B are often due to infected blood, unprotected sex or mother-to-child transmission during birth. Unlike newborns, most untreated, newly infected adults clear the infection.

In San Francisco, hepatitis B is common because of the large Asian-American population in which the disease has been passed down from mother to newborn over many generations. A goal of the Health and Human Services action plan is to eliminate mother-to-child transmission.

Hepatitis C is transmitted most easily through exposure to infected blood, and compared to hepatitis B is more apt to become a chronic infection in newly infected adults.

Nationwide, hepatitis C virus has surpassed HIV as a cause of death, according to a U.S. Centers for Disease Control and Prevention (CDC) report published earlier this year. Injection drug users may be at greater risk of being infected with hepatitis C than with human immunodeficiency virus (HIV). Millions of baby boomers were infected before testing became available to screen blood products.

In May, the CDC proposed draft recommendations calling for people in the U.S. born between 1945 and 1965 to be screened for hepatitis C. In the U.S., more than 1 million in this age group are believed to be unknowingly, chronically infected.

Although hepatitis C infection rates have dropped considerably, infection is still epidemic among injection drug users. HIV prevention has led to lower rates of infection, but still more than half of injection drug users are infected with hepatitis C. Locally, prevention, testing and counseling for hepatitis C have become public health priorities.

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More than 1/4 L.A. homeless adults have hepatitis C


Nearly 1/2 don’t know it.

Lillian Gelberg, UCLA

Recent government studies show that hepatitis C, which can destroy the liver and necessitate a liver transplant, now kills more American adults than AIDS, and new UCLA research shows just how prevalent the disease is among homeless adults in downtown Los Angeles.

In a study published in the July–August issue of Public Health Reports, researchers found that 26.7 percent of homeless adults tested and surveyed in downtown Los Angeles’ skid row were infected with the hepatitis C virus (HCV) — more than 10 times the 2 percent rate among the general U.S. population. Of those surveyed, 46.1 percent were unaware that they were infected. Four percent of the sample were HIV-positive.

Few of the infected homeless adults surveyed had ever received any treatment for their HCV, said Dr. Lillian Gelberg, professor of family medicine at the David Geffen School of Medicine at UCLA, who led the study with Dr. Marjorie Robertson of the Public Health Institute’s Alcohol Research Group. Less than 3 percent of those who knew they were infected had ever been treated.

“Their hepatitis C can result in high costs to the public and the health care system if progression of their disease is not halted through treatment,” said Gelberg, who is also a professor of public health at the UCLA Fielding School of Public Health. “The costs of their untreated hepatitis C may start escalating soon, as many are approaching 20 years of infection, which is the point at which we see escalating risk for liver cirrhosis and end-stage liver disease, requiring expensive health services utilization and liver transplantation.”

The study surveyed 534 homeless adults from 41 shelters and meal programs in the skid row area between June 2003 and February 2004. Most were males and the majority were African Americans. Each was tested for hepatitis B and C and for HIV. Overall, the researchers found that HCV prevalence was significantly higher among those homeless individuals who had injected drugs or been in prison; who were 40 years of age and older; who had less education; or who were U.S.-born.

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Scarring cells revert to inactive state as liver heals


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.

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Modest alcohol use lowers risk, severity of some liver disease


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.

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Combined Health Agencies honors four UC San Diego health heroes


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.

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Hepatitis C is frequently undiagnosed but often curable


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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Migrating cells ‘turn right’


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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