“This is another, potentially highly efficacious way to block replication of hepatitis C.”

Samuel French, UCLA

Researchers from UCLA’s Jonsson Comprehensive Cancer Center have identified a cell-permeable peptide that inhibits a hepatitis C virus protein and blocks the viral replication that can lead to liver cancer and cirrhosis.

The finding by Dr. Samuel French, a UCLA assistant professor of pathology and senior author of the research, builds on previous work by French’s laboratory that identified two cellular proteins that are important factors in hepatitis C virus infection.

In that earlier research, French and his team set out to identify the cellular factors involved in hepatitis C replication. Using mass spectrometry, they found that heat-shock proteins (HSPs) 40 and 70 were important for viral infection. HSP 70 was previously known to be involved, but the study linked HSP 40 for the first time to hepatitis C infection. The researchers further showed that the natural compound quercetin, which inhibits the synthesis of these proteins, significantly inhibited viral infection in tissue culture.

In the current study, published Jan. 30 in the peer-reviewed journal Hepatology, French and his team demonstrated that the viral, non-structural protein 5A (NS5A) directly binds to HSP 70, and they mapped the site of the NS5A–HSP 70 complex on NS5A. While HSP 70 was previously shown to bind to NS5A in cells, a direct NS5A–HSP70 interaction and complex formation was established in this study. In an effort to stop this interaction, the researchers tested peptides that might inhibit HSP 70.

“This is important because we’ve developed a small peptide which binds to that site and blocks the interaction between the proteins that is important for viral replication,” French said. “This is another, potentially highly efficacious way to block replication of hepatitis C.”

An estimated 160 million people worldwide are infected with hepatitis C, and the conventional treatments — interferon and ribavirin — can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, French said.

“We were surprised that this peptide works this well,” he said. “While its mechanism is different, the activity of this peptide is comparable to other newly developed antivirals.”

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SF HIP aims to connect UCSF’s research capital with community partners to improve health.

UCSF's Kevin Grumbach (left) and Laura Schmidt (right) at SF HIP coordinating council meeting

UC San Francisco and an array of community, academic and civic collaborators are wrapping up the first year of an ambitious effort to build partnerships to enhance the well-being of San Francisco residents and eliminate health disparities.

San Francisco Health Improvement Partnerships (SF HIP), a cross-cutting initiative of the UCSF Clinical and Translational Science Institute (CTSI), aims to connect the university’s research capital with the expertise and needs of community partners. The goal is to implement strategies to measurably impact health in San Francisco — and to promote health equity along the way.

“In the past, research has often been seen as unilaterally serving the needs of the researchers rather than the community,” said Kevin Grumbach, M.D., co-director of CTSI’s Community Engagement and Health Policy (CEHP) Program. “SF HIP is an effort to do it differently; to have the outcome not be theoretical, but rather a discrete and sustainable change in community health.”

SF HIP is conducted in a spirit of participatory research with oversight by its Coordinating Council. Community partners include representatives from CTSI, the San Francisco Department of Public Health, San Francisco Unified School District, San Francisco Hospital Council, Mayor’s Office of Housing and Community Development, and health equity coalitions representing the African American, Latino and Asian/Pacific Islander communities. CTSI’s CEHP program serves as the administrative core of the initiative and provides planning funds.

“SF HIP brings UCSF and its resources closer to the community, and all the important stakeholders together to improve community health,” said Amor Santiago, DPM, MPH, executive director of APA Family Support Services, and representative of the Asian/Pacific Islander Health Parity Coalition on the SF HIP Coordinating Council. “This effort has the potential to lead and coordinate public health efforts across the spectrum of providers in medical, mental and social health emphasizing prevention.”

So far, SF HIP working groups have been launched to focus on four pressing needs: physical activity and nutrition, hepatitis B, alcohol abuse and dental caries in children.

“Part of this effort involves laying a foundation for long-term collaboration,” said Ellen Goldstein, M.A., program manager of the CEHP program. “That includes developing an ongoing framework for UCSF to productively engage with a wide range of community partners to tackle our city’s most compelling health problems.”

[Related: View more about UCSF's commitment to the community]

SF HIP is part of UCSF’s expansive community service efforts that span outreach in local, regional and global communities.

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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.

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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Rubik’s Cubes, Pokemon, Furbies…. The average UC Davis student can name the one trend that has triumphed over even these favorites, remaining in popular culture for thousands of years: tattoos.

But as trendy (and long-standing) as tattoos are, they can also be dangerous, leading to the hepatitis C virus. The Be Smart with Body Art campaign launched in December 2009 by the UC Davis Cancer Center and Sacramento State has made it its mission to educate students. The campaign addresses the fact that there are currently no standardized statewide health codes for piercings or tattoos.

“Young people need to know about the hepatitis C virus and all the ways it can be transmitted, including through tattooing and body piercing,” says Marlene von Friederichs-Fitzwater, a faculty member of the UC Davis School of Medicine and director of the Outreach Research and Education Program at the UC Davis Cancer Center.

“It’s not only a disease of IV drug users — millions of people are infected today and don’t know it.”

Hepatitis C is a liver disease caused by the hepatitis C virus that sometimes results in an acute illness, but most often becomes a silent, chronic infection that can lead to cirrhosis (scarring), liver failure or cancer, and death, according to the National Prevention Information Network. It is spread by contact with the blood of an infected person. There is currently no vaccine.

More than 40 percent of college students at UC Davis and Sacramento State aren’t aware of the risks, according to a survey done by the campaign coordinators, von Friederichs-Fitzwater of UC Davis and Heather Diaz of Sacramento State.

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More than 40 percent of college students falsely believe that tattooing and body piercing are unlikely to pose health risks, researchers from UC Davis and Sacramento State University have found.The two universities have teamed up to address the lack of awareness with an innovative new multimedia campaign that educates young people about ways to prevent spread of viral hepatitis C when getting tattoos or piercings.

Be Smart with Body Art is a project of the UC Davis Cancer Center-Sacramento State University Partnership, in association with young adult cancer survivors and tattoo and piercing professionals. The campaign launched today aims to raise awareness that body art done improperly can lead to the spread of viral blood diseases such as hepatitis C, a disease that is only successfully treated in about 50 percent of cases. And it will arm young people with questions to ask the artist before getting a tattoo or piercing.

“We want to give accurate information about safe tattooing that individuals can use themselves and share with others,” said Marlene von Friederichs-Fitzwater, a faculty member with the UC Davis School of Medicine and Cancer Center. “The hepatitis C virus can lead to liver disease and liver cancer, and our goal is to prevent new infections by informing young adults of all the ways it can be transmitted.”

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