July 26, 2013

Prevention and Management of Hepatitis C Virus Infection Among People Who Inject Drugs: Moving the Agenda Forward

Provided by NATAP

All PDFs attached

Clinical Infectious Diseases
Volume 57 suppl 2 August 15, 2013

- Moving the Agenda Forward: The Prevention and Management of Hepatitis C Virus Infection Among People Who Inject Drugs
Jason Grebely, Philip Bruggmann, Markus Backmund, and Gregory J. Dore
Moving the Agenda Forward: The Prevention and Management of Hepatitis C Virus Infection Among People Who Inject Drugs

- Injection Drug Use and Hepatitis C Virus Infection in Young Adult Injectors: Using Evidence to Inform Comprehensive Prevention
Kimberly Page, Meghan D. Morris, Judith A. Hahn, Lisa Maher, and Maria Prins
Injection Drug Use and Hepatitis C Virus Infection in Young Adult Injectors: Using Evidence to Inform Comprehensive Prevention

- Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy
Natasha K. Martin, Matthew Hickman, Sharon J. Hutchinson, David J. Goldberg, and Peter Vickerman
Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy

- Hepatitis C Virus Vaccines Among People Who Inject Drugs
Andrea L. Cox and David L. Thomas
Hepatitis C Virus Vaccines Among People Who Inject Drugs

- Understanding Barriers to Hepatitis C Virus Care and Stigmatization From a Social Perspective
Carla Treloar, Jake Rance, and Markus Backmund
Understanding Barriers to Hepatitis C Virus Care and Stigmatization From a Social Perspective

- Models of Care for the Management of Hepatitis C Virus Among People Who Inject Drugs: One Size Does Not Fit All
Philip Bruggmann and Alain H. Litwin
Models of Care for the Management of Hepatitis C Virus Among People Who Inject Drugs: One Size Does Not Fit All

- Assessment and Treatment of Hepatitis C Virus Infection Among People Who Inject Drugs in the Opioid Substitution Setting: ETHOS Study
Maryam Alavi, Jason Grebely, Michelle Micallef,, Adrian J. Dunlop,, Annie C. Balcomb, Carolyn A. Day, Carla Treloar, Nicky Bath, Paul S. Haber, Gregory J. Dore, and on behalf of the Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) Study Group
Assessment and Treatment of Hepatitis C Virus Infection Among People Who Inject Drugs in the Opioid Substitution Setting: ETHOS Study

- Enhancing Assessment and Treatment of Hepatitis C in the Custodial Setting Jeffrey J. Post, Amber Arain, and Andrew R. Lloyd
Enhancing Assessment and Treatment of Hepatitis C in the Custodial Setting

- Peer Support Models for People With a History of Injecting Drug Use Undertaking Assessment and Treatment for Hepatitis C Virus Infection
Sione Crawford and Nicky Bath
Peer Support Models for People With a History of Injecting Drug Use Undertaking Assessment and Treatment for Hepatitis C Virus Infection

- Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis
Esther J. Aspinall, Stephen Corson, Joseph S. Doyle, Jason Grebely, Sharon J. Hutchinson, Gregory J. Dore, David J. Goldberg, and Margaret E. Hellard
Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

- Directly Observed Pegylated Interferon Plus Self-Administered Ribavirin for the Treatment of Hepatitis C Virus Infection in People Actively Using Drugs: A Randomized Controlled Trial
Robert J. Hilsden, Gisela Macphail, Jason Grebely, Brian Conway, and Samuel S. Lee
Directly Observed Pegylated Interferon Plus Self- Administered Ribavirin for the Treatment of Hepatitis C Virus Infection in People Actively Using Drugs: A Randomized Controlled Trial

- Psychoeducation Improves Hepatitis C Virus Treatment During Opioid Substitution Therapy: A Controlled, Prospective Multicenter Trial
Jens Reimer, Christiane Sybille Schmidt, Bernd Schulte, Dirk Gansefort, Jorg Golz, Guido Gerken, Norbert Scherbaum, Uwe Verthein, and Markus Backmund
Psychoeducation Improves Hepatitis C Virus Treatment During Opioid Substitution Therapy: A Controlled, Prospective Multicenter Trial

- Hepatitis C Virus Reinfection Following Treatment Among People Who Use Drugs
Bart P. Grady, Janke Schinkel, Xiomara V. Thomas, and Olav Dalgard
Hepatitis C Virus Reinfection Following Treatment Among People Who Use Drugs

- Management of Mental Health Problems Prior to and During Treatment of Hepatitis C Virus Infection in Patients With Drug Addiction
Martin Schaefer, Rahul Sarkar, and Crisanto Diez-Quevedo
Management of Mental Health Problems Prior to and During Treatment of Hepatitis C Virus Infection in Patients With Drug Addiction

- Drug-Drug Interactions in the Treatment of HCV Among People Who Inject Drugs Stefan Mauss and Hartwig Klinker
Drug-Drug Interactions in the Treatment of HCVAmong People Who Inject Drugs

- Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs
Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs

Geert Robaeys, Jason Grebely, Stefan Mauss, Philip Bruggmann, Joseph Moussalli, Andrea De Gottardi, Tracy Swan, Amber Arain, Achim Kautz, Heino Stover, Heiner Wedemeyer, Martin Schaefer, Lynn Taylor, Markus Backmund, Olav Dalgard, Maria Prins, Gregory J. Dore, and on behalf of the International Network on Hepatitis in Substance Users


T-Cells May Show HCV Exposure in Healthcare Workers With Negative Antibodies

Reuters Health Information

Jul 15, 2013

By Robert Goodier

NEW YORK (Reuters Health) Jul 15 - Measuring T-cell responses reveals exposure to hepatitis C in healthcare workers who test negative for antibodies against the virus, a new study has found.

T-cell proliferation assays may be a more sensitive test, the results suggest. But the low-level exposures that the assays can detect are highly unlikely to be a health risk for the patient or for others, according to experts who spoke to Reuters Health.

Rather, the results suggest that T-cell assays should be included in surveillance studies that monitor exposure to hepatitis C, said Dr. Barbara Rehermann, Chief of the Immunology Section of the Liver Diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, in email to Reuters Health.

Dr. Rehermann and her team published their research online June 28 in the Journal of Infectious Diseases.

They performed T-cell assays on samples from 72 healthcare workers who had been in contact with a source of the virus, most of them through an accidental stick by a contaminated needle. During six months of follow-up, none of the workers tested positive for a chronic hepatitis C infection, but nearly half had evidence of an immune response to the virus, denoted by white blood cells, not by antibodies.

"Part of the interest of this study is we're learning more about how our bodies control viruses and how quickly we're able to respond to them," said Dr. Henry Bodenheimer at Beth Israel Medical Center in New York City, who was not involved in the research.

"It seems that very low level infection can be controlled by our immune systems. That's new information. Much of the time people have relied on antibodies. Studying T-cells is a more difficult, but a novel approach," Dr. Bodenheimer told Reuters Health.

The findings may lead to new approaches to vaccine development or treatments that stimulate the immune response to fight hepatitis infection, Dr. Bodenheimer said.

But, he added, this study does not suggest that testing methods should be changed. Antibody tests can detect chronic infection, but there is no evidence that the infection detected by T-cell assays was transmissible or linked to long-term consequences in the healthcare workers, Dr. Bodenheimer pointed out.

Past studies have offered a range of estimates of the risk of transmission of the virus to exposed healthcare workers, from 0 to 10.3%, with an average of 0.5%, according to a 2005 report in Clinical Infectious Diseases (see http://bit.ly/15g4une). The reason for that variation is not clear, however.

In this new study, assays of peripheral blood mononuclear cells in proliferation found hepatitis C-specific T-cell responses in 30 out of 63 participants tested, or 48%.

Interferon-gamma enzyme assays found at least two hepatitis-specific responses in 26 out of 62 participants tested, or 42%.

Fifty-three subjects underwent both tests. Thirteen (24%) responded to both, 21 (40%) did not respond to either, and 19 (36%) responded to one but not the other.

Those who were exposed to the virus after high-risk, rather than low-risk, needle sticks had higher proliferative T-cell responses.

"Whether these T-cell responses reflect protective immunity or whether they are downstream events of protective innate immune responses or abortive replication of defective viral genomes requires further studies in suitable models," Dr. Rehermann and her team write.

In the general population, the Centers for Disease Control and Prevention now recommends that all Baby Boomers, those born from 1945 to 1965, be tested for hepatitis C.

SOURCE: http://bit.ly/15g7cZW

J Infect Dis 2013.


Fever After Interferon Injection for HCV Predicts Treatment Success

Reuters Health Information

Jul 25, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Jul 25 - Patients with chronic hepatitis C virus (HCV) who become febrile after peginterferon alfa-2a (PEG-IFN) injection are more likely to have a virological response than those who don't, a retrospective study suggests.

"Many patients find it difficult to complete interferon-based regimens because of the side-effects," Dr. Yaron Rotman from National Institutes of Health, Bethesda, Maryland told Reuters Health by email. "Clinicians can use our findings as a tool to encourage patients who suffer from side effects, to let them know that these actually suggest they are responding, and to help convince them to persist and maintain their compliance and adherence to treatment."

Fever commonly follows PEG-IFN injection, but the factors that predict the magnitude of this febrile response and its association with the antiviral efficacy of PEG-IFN are unknown.

To explore this issue, Dr. Rotman and colleagues reviewed data from a prospective trial of 60 treatment-naive adults with chronic HCV.

Most (57%) were infected with genotype 1, and their average age was 52 years.

As reported online July 11th in the Journal of Hepatology, oral temperature rose above 38.0 C in 20 patients (33%) at a median of 12.5 hours after injection.

The maximum temperature increase correlated strongly with the first phase virological decline, with a 0.49 C increase for each 1 log10 decline in viral levels.

Temperature increases did not differ significantly by gender. The link between temperature increase and virological decline also didn't differ by gender, nor by the presence or absence of cirrhosis or the viral genotype.

The maximum temperature change was higher for patients with the IL28B-related SNP rs12979860 CC genotype, and the correlation of maximum temperature increase with virological decline was limited to patients with the CC genotype.

Despite the link of temperature change with virological response, maximum temperature change did not predict either rapid or sustained virological response very well, and it was only a weak predictor of early virological response.

"Since the spike of fever is independent of virological predictors of response, it could potentially serve in the research setting as a tool to tease out host interferon-responsiveness from viral- and liver-related factors," the researchers say.

"The clinical importance of the study is in the novel appreciation that medication side-effects are closely linked to its efficacy," Dr. Rotman said.

"Of course," he continued, "the interferon-induced fever is not causing viral clearance, and we are not claiming that, but its occurrence early on (in the first 24 hours) can give patients and their doctors an inclination that the drug is actually doing its job."

Dr. Hans Van Vlierberghe from Ghent University Hospital in Belgium, who has published work on chronic HCV treatment, told Reuters Health by email, "This is a very nice and elegant study, monitoring temperature after peginterferon administration and linking the rise in temperature to response. However, treatment of hepatitis C is evolving more and more to an interferon-free combination schedule, making the observation by the authors less and less relevant."

Dr. Rotman added, "I would have to credit the first author, Hwalih Han, BSN, BS, the research nurse specialist, who has done a significant amount of the work on this study under my mentorship. Research nurses are not typically involved in the analysis and writing of clinical trial manuscripts; our work shows how physicians and nurses can work in synergy not only in clinical care, but also in research, especially in areas that straddle both disciplines."

SOURCE: http://bit.ly/172Njoy

J Hepatol 2013.


Marijuana May Not Exacerbate Liver Disease in At-Risk Patients

Reuters Health Information

Jul 25, 2013

By Rob Goodier

NEW YORK (Reuters Health) Jul 25 - Marijuana smoking doesn't appear to accelerate liver disease progression in HIV patients with hepatitis C coinfection, a new prospective study from Canada has found.

"Based on previous studies, physicians have counseled patients that marijuana is harmful to their livers," Dr. Marina Klein, of McGill University Health Centre in Montreal, told Reuters Health by email.

"The results of our study suggest that physicians can reassure their patients that marijuana use, while it may have other deleterious effects, likely will not make their liver disease progress more rapidly," said Dr. Klein, who led the study, published online June 28 in Clinical Infectious Diseases.

Patients in Canada can apply for permission to use marijuana for medicinal purposes. The United States has conflicting marijuana laws. The federal government outlaws it, but 18 states allow for medicinal use, including two, Colorado and Washington, that also allow for recreational use.

The researchers followed up with 690 patients at 17 Canadian HIV clinics for an average of 2.7 years. The patients had HIV-hepatitis C coinfection at baseline, but did not have significant liver fibrosis (aspartate aminotransferase-to-platelet ratio (APRI) < 1.5).

At baseline, more than half of the patients said they had smoked marijuana in the past six months (median, seven joints per week) and 40% of those did so daily. A similar proportion said they used the drug for symptom relief.

In the course of the study, 19% of the patients reached an APRI score of 1.5, and 15% percent progressed to a score of 2. Eight patients, representing 1.2% of the study group, developed cirrhosis and 11, or 1.6%, developed end-stage liver disease (ESLD).

On multivariate analysis, there was no link between marijuana smoking and progression to liver disease based on the APRI score.

The researchers did find an association between marijuana use and progression to a clinical diagnosis of cirrhosis, with a hazard ratio of 1.33 per 10 additional joints per week. But when they reevaluated the findings using a lagged model of marijuana exposure, the association became statistically insignificant.

The lagged model measured marijuana use six to 12 months before the period during which liver disease developed, while the main model measured marijuana use during the same time that liver disease was diagnosed.

"The idea, really, was to make sure that smoking started before the participants got a liver problem and using the exposure and outcome at the same interval doesn't allow that (e.g. patients may have simply increased their use because they had symptoms of a disease that was already present). When we did this, it no longer looks as though marijuana is associated with any of the outcomes we investigated," Dr. Klein said.

That bias may explain some of the associations found between marijuana use and liver disease in past studies, she added.

SOURCE: http://bit.ly/12LdD5o

Clin Infect Dis 2013.


Proclamation -- World Hepatitis Day, 2013

The White House

Office of the Press Secretary

For Immediate Release

July 25, 2013


- - - - - - -



Each year, we mark World Hepatitis Day to bring attention to a disease that afflicts one in twelve people worldwide. Viral hepatitis is a major cause of liver cancer and cirrhosis in the United States, leading to approximately 18,000 American deaths every year. Outcomes can significantly improve with treatment, but because viral hepatitis can be present without symptoms for decades, most infected Americans do not know they have it. Today, we raise awareness about preventing and treating viral hepatitis, and we renew our commitment to combat this disease in all its forms.

Public awareness is key to halting the spread of viral hepatitis. All types of this disease pose serious health threats, and both hepatitis B and C can become chronic infections that lead to liver cancer and liver disease. Vaccines for hepatitis A and B are crucial to preventing new cases, and they are recommended for all children, as well as adults at an elevated risk of infection. There is no vaccine against hepatitis C, but through early detection and treatment, it is possible to reduce the risk of transmission, avert the worst complications, and in many cases even cure the infection.

Anyone can contract hepatitis, but in the United States it disproportionately affects the African American, Hispanic, and Asian American and Pacific Islander communities, and people born between 1945 and 1965. Injection drug users of all ages are also at increased risk. My Administration is working to raise awareness among communities hardest hit by viral hepatitis, organizing campaigns to prevent new infections, and promoting testing and treatment.

My Administration also continues to work with our partners across the Federal Government, in States, communities, and the public and nonprofit sectors to implement programs like the Healthy People 2020 initiative and the Action Plan for the Prevention, Care, and Treatment of Viral Hepatitis. This ambitious plan aims to reduce the number of new hepatitis C cases by 25 percent, eliminate mother-to-child transmission of hepatitis B, and significantly increase the proportion of people who know of their hepatitis B and C infections. In addition, the Affordable Care Act requires health insurance plans to cover, without co-pays, hepatitis A and B vaccines as recommended for children and adults at elevated risk for infection, as well as hepatitis B screenings for pregnant women at their first prenatal visit. After June 2014, new health plans must cover screening, without co-pays, for hepatitis C virus infection in persons at high risk for infection. Plans must also cover one-time screening for hepatitis C infection for adults born between 1945 and 1965.

Viral hepatitis is a silent epidemic, and we can only defeat it if we break that silence. Now is the time to learn the risk factors for hepatitis, talk to family, friends, and neighbors who may be at risk, and to speak with healthcare providers about strategies for staying healthy. On World Hepatitis Day, let each of us lend our support to those living with hepatitis and do our part to bring this epidemic to an end.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim July 28, 2013, as World Hepatitis Day. I encourage citizens, Government agencies, nonprofit organizations, and communities across the Nation to join in activities that will increase awareness about hepatitis and what we can do to prevent it.

IN WITNESS WHEREOF, I have hereunto set my hand this twenty-fifth day of July, in the year of our Lord two thousand thirteen, and of the Independence of the United States of America the two hundred and thirty-eighth.



Hepatitis C: 6 Prevention Strategies That Work

Medscape Medical News

Ricki Lewis, PhD

Jul 26, 2013

Hepatitis C virus (HCV) infection is on the rise, particularly among young white adults living in rural and suburban areas who abuse intravenous opiate drugs. A review article published in a special supplement to Clinical Infectious Diseases, coinciding with World Hepatitis Week, discusses 6 ways to combat the spread of HCV in this group.

HCV incidence is increasing among those aged 15 to 30 years who inject drugs, according to the US Department of Health and Human Services. HCV is 10 times as infectious as HIV and surpassed HIV in number of deaths in the United States in 2007. Nearly 4 million people in the United States have chronic HCV infection.

For 16 years, Kimberly Page, PhD, MPH, from the University of California, San Francisco, and colleagues have conducted the "U Find Out," or UFO, Study with injection-drug users. The program is modeled on clean syringe programs, but with greater emphasis on social issues that fuel drug abuse and on integrating multiple approaches to combat HCV infection. Data from the ongoing prospective study show that the interventions used can reduce the risk of seroconversion.

In addition, the investigators note that more than 31,000 young adults who inject drugs of abuse will become infected with HCV in the United States each year. "Although there is evidence that HCV incidence has declined in recent decades, if the number of young injectors increases, as the [Centers for Disease Control and Prevention] suggests is occurring in the United States, these gains could be lost. Ongoing and targeted surveillance efforts to enumerate the population at risk and assess the burden of infection are essential steps in targeting and implementing effective HCV prevention in this group," the authors write.

Therefore, they recommend 6 comprehensive measures to prevent the spread of hepatitis C:

  1. Reducing risk from shared ancillary drug preparation equipment, such as containers, rinse water, and filters. The researchers estimate that paying attention to the ancillaries as well as shared syringes could prevent at least 25% of seroconversions. The availability of single-use supplies could lower risk.

  2. Using a new rapid test at point of care that offers results in 20 minutes can detect infection before seroconversion and, combined with counseling, can help to stem transmission.

  3. Addressing social and relational contexts of injecting can encourage uninfected individuals to take precautions when injecting drugs with infected sex partners.

  4. Encouraging "taking a break" from injecting drugs because HCV cannot be transmitted without this behavior. In past studies, the investigators discovered that the more often drug abusers attempted to quit, the more likely they were to eventually succeed.

  5. Developing models to guide delivery of new prevention strategies, including already-available approaches such as increasing syringe availability and future strategies such as direct-acting antivirals that can be used prophylactically, as well as vaccines.

  6. Combining interventions in synergistic ways, such as needle exchange and methadone maintenance programs.

"With ongoing and expanding transmission of HCV, there is little doubt that there is a need to implement what is in the prevention 'toolbox,' as well as add to it," they write. "Expanding HCV prevention and reaching the new generation of young injectors will require dedicated advocacy, pragmatism, and persistence to enable access to all of these technologies."

The work was supported by the National Institute on Drug Abuse. The Kirby Institute is funded by the Australian Government Department of Health and Ageing. One coauthor is also supported by a National Health and Medical Research Council Senior Research Fellowship. The other authors have disclosed no relevant financial relationships.

Clin Infect Dis. 2013;57:S32-S38. Abstract


Also See:

  1. Miriam researcher helps develop global hepatitis C recommendations for injection-drug users
  2. Six Recommended Measures to Prevent Hepatitis C for Young Injection-Drug Users
  3. Moving the Agenda Forward: The Prevention and Management of Hepatitis C Virus Infection Among People Who Inject Drugs

New focus to combat rising liver disease


Friday, 26 July 2013

University of Adelaide researchers are investigating how the liver responds to hepatitis C virus (HCV) and why some people can control the virus while others can't. The aim is to find better therapies to combat hepatitis C and associated liver disease.

Speaking ahead of World Hepatitis Day (Sunday 28 July), Head of the Hepatitis C Virus Research Laboratory Associate Professor Michael Beard says the burden of disease from the hepatitis C virus is rapidly escalating.

"A large number of people were infected with HCV in the 1970s and 1980s before isolation of the virus in 1989, and we're now seeing those people emerging with liver disease," says Associate Professor Beard. "Unfortunately, liver cancer as a result of HCV infection is on the rise and is expected to double by 2020."

HCV is blood-borne and contracted primarily through injecting drug use and, before bloodbank screening for HCV started in 1990, through blood-transfusion. Unchecked hepatitis C can lead to chronic disease and liver cancer and there are currently more than 220,000 Australians living with chronic hepatitis C.

A unique feature of infection with HCV is that about 75% of individuals develop a chronic infection while 25% spontaneously clear the virus.

"We hope to understand why some people can combat the virus without drugs and why others can't," says Associate Professor Beard. "We'll be looking at how the liver cells respond to HCV infection to see how genes are being regulated and how this, in turn, impacts virus replication and liver disease."

"If we can better understand this process, we will be able to use this information to help develop a vaccine or improved antiviral drugs." Vaccines exist for hepatitis A and B, but not for hepatitis C.

The Adelaide researchers will be using live imaging of the virus in cultured liver cells to investigate the interactions between the liver cell and the virus in real time.

"Up until now, we've only been able to look at virus infection in a particular snap-shot in time. Now we can look at the dynamics between the cell and the virus, within a living cell," Associate Professor Beard says.

"We're also investigating how some of the emerging new classes of antiviral drugs work and what their mode of action is. This will help develop the next generation of antiviral drugs against HCV."

The research is funded by the National Health and Medical Research Council (NHMRC) under a $5.5 million program grant with University of Sydney and University of NSW, starting in 2014.

Associate Professor Beard is also convenor of the 20th International Symposium on Hepatitis C Virus and Related Viruses which meets in Melbourne in October and will discuss the latest knowledge in hepatitis therapies and disease.


FDA puts ‘partial hold’ on Vertex study

By Robert Weisman | Globe Staff  July 25, 2013

Federal regulators have put a “partial clinical hold” on a mid-stage study of an experimental oral drug developed by Vertex Pharmaceuticals Inc. to treat hepatitis C.

The move will prevent the Cambridge company from giving clinical trial patients 200 milligram doses of the pill, which would be used in combination with other oral therapies to treat the virus.

Vertex already has an oral hepatitis C treatment on the market, but it is used in combination with an injectable drug.

A Vertex spokesman, Zach Barber, said that the Food and Drug Administration ordered the hold after three patients in a European trial showed elevated liver enzymes — a potential marker of liver damage — when taking 400 milligram doses.

The US trial was designed to use only 100 milligram and 200 milligram dosing levels, he said. Vertex will continue with its 100 milligram dosing.

“The FDA has requested data from us, and we’ll be providing that data on an ongoing basis” to gauge the effect of the drug candidate on patients, Barber said. “Hepatitis C remains an important part of our business and with multiple ongoing studies of [the experimental pill], our strategy is unchanged.”

Robert Weisman can be reached at weisman@globe.com. Follow him on Twitter @GlobeRobW.


Also See: Vertex Provides Update on Ongoing All-Oral Studies of VX-135 in Hepatitis C

Leading Liver and ID Experts to Develop Hepatitis C Practice Recommendations

Provided by Infection Control Today

Recognizing the rapid development of hepatitis C medications coupled with increasing numbers of people being identified with hepatitis C virus (HCV) infection, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) are collaborating to develop clinical recommendations for the management of hepatitis C. 

New medications approved by the Food and Drug Administration in recent  years have increased HCV cure rates, and several additional medications are expected to be approved  in the next three to five years. At the same time, new HCV testing guidelines are expected to increase the number of patients diagnosed with hepatitis C, many of whom currently are HCV-infected but unaware of their status. Ensuring that patients receive the new, effective treatment will be critical in increasing cure rates for hepatitis C.

“We can finally say that cure of HCV infection has become a real possibility for the majority of individuals infected with this deadly virus,” says Gary Davis, MD, of AASLD.
“Members of AASLD and IDSA are committed to ensuring that patient care keeps pace with rapidly advancing science,” said David Relman, MD, president of IDSA. “This effort is an important step toward advancing that goal and comes at an important time as we all work to raise awareness of hepatitis virus infections on World Hepatitis Day on July 28.”

Through this collaboration, the societies will review current treatment recommendations and use evidence-based, consensus guidance to develop updated recommendations for managing patients. Recommendations will be updated regularly and made available online. “A web-based system of new recommendations coupled with a published annual update will afford the greatest opportunity for both rapid and comprehensive output,” says Donald M. Jensen, MD, of AASLD.

Hepatitis C is a liver disease resulting from chronic infection with the hepatitis C virus (HCV).  It is estimated that between 3 million and 4 million Americans are infected with HCV and have chronic liver disease as a result. Because symptoms of HCV infection may not appear for many years, more than 70 percent are unaware they are infected.

Earlier this year, the Centers for Disease Control and Prevention recommended an age-based screening strategy consisting of a one-time test for HCV for those at highest risk, including everyone born between 1945 and 1965. This recommendation was endorsed by the U.S. Preventive Services Task Force in June 2013. The broader testing recommendations likely will detect a substantial number of people who are unaware they are infected.

According to a July 10, 2013 article published in the Journal of The American Medical Association (JAMA), deaths from liver disease increased from 1990 to 2010. HCV is the most likely cause of the emergence of liver disease as a growing threat to Americans. Early testing enables people who are infected to receive treatment as soon as possible, and prevent progression to more serious disease, such as cirrhosis and liver cancer.

Currently available drugs and the next generation of direct-acting antivirals that will likely be available later this year offer the potential to treat and cure most patients with HCV infection. Therefore, up-to-date recommendations for the medical management of these patients and their treatment are critically important.


Human stem cell-derived hepatocytes regenerate liver function

Public release date: 26-Jul-2013
Contact: Vicki Cohn
914-740-2100 x2156
Mary Ann Liebert, Inc./Genetic Engineering News

And extend survival in mice with hepatic failure

New Rochelle, NY, July 26, 2013 -- Researchers have generated functional hepatocytes from human stem cells, transplanted them into mice with acute liver injury, and shown the ability of these stem-cell derived human liver cells to function normally and increase survival of the treated animals. This promising advance in the development of cell-based therapies to treat liver failure resulting from injury or disease relied on the development of scalable, reproducible methods to produce stem cell-derived hepatocytes in bioreactors, as described in an article in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Stem Cells and Development website.

Massoud Vosough and coauthors demonstrate a large-scale, integrated manufacturing strategy for generating functional hepatocytes in a single suspension culture grown in a scalable stirred bioreactor. In the article "Generation of Functional Hepatocyte-Like Cells from Human Pluripotent Stem Cells in a Scalable Suspension Culture" the authors describe the method used for scale-up, differentiation of the pluripotent stem cells into liver cells, and characterization and purification of the hepatocytes based on their physiological properties and the expression of liver cell biomarkers.

David C. Hay, MRC Centre for Regenerative Medicine, University of Edinburgh, U.K., comments on the importance of Vosough et al.'s contribution to the scientific literature in his editorial in Stem Cells and Development entitled "Rapid and Scalable Human Stem Cell Differentiation: Now in 3D." The researchers "developed a system for mass manufacture of stem cell derived hepatocytes in numbers that would be useful for clinical application," creating possibilities for future "immune matched cell based therapies," says Hay. Such approaches could be used to correct mutated genes in stem cell populations prior to differentiation and transplantation, he adds.

"The elephant in the room for stem cell therapy rarely even acknowledged let alone addressed in the literature is that of scalable production of cells for translational application," says Editor-in-Chief Graham C. Parker, PhD, research professor, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine. "Baharvand's groups' landmark publication not only demonstrates but exquisitely describes the methodology required to scale up stem cell populations for clinical application with a rigor to satisfy necessary manufacturing standards."


About the Journal

Stem Cells and Development is an authoritative peer-reviewed journal published 24 times per year in print and online. The Journal is dedicated to communication and objective analysis of developments in the biology, characteristics, and therapeutic utility of stem cells, especially those of the hematopoietic system. Complete tables of content and a free sample issue may be viewed on the Stem Cells and Development website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Cellular Reprogramming, Tissue Engineering, and Human Gene Therapy. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 Phone: (914) 740-2100 (800) M-LIEBERT Fax: (914) 740-2101 http://www.liebertpub.com


World Hepatitis Day: When in Doubt Get Tested


July 24, 2013

The following statement was issued by the BCCDC and BC Centre of Excellence for HIVAIDS to mark World Hepatitis Day, July 28.

By Dr. Mel Krajden and Dr. Julio Montaner

Hepatitis is a frequent headline-maker in media, and creates lots of online chat in blogs, tweets and posts. No wonder, given that this liver disease is potentially life-threatening. Despite all this attention, getting people tested and treated is still a challenge for public health practitioners.

As we acknowledge the annual World Hepatitis Day on July 28, the number of infections is still of concern.  One in 12 people worldwide has liver disease, and greater than three per cent, or more than 120,000 people in BC are hepatitis B and/or C-infected.

Enormous strides in hepatitis B prevention have been made in the province through the use of publically-funded vaccinations covering all children. However, hepatitis C is a different story.

There is so far no vaccine for this silent killer, which can lay dormant for decades, often only showing symptoms when much damage is done. Two thirds of all cases are “baby boomers” born between 1945 and 1965 - people who should be in their peak earning and family-raising years. Instead, many of their years are spent with increasing disabilities because of this disease.

The earlier hepatitis C is detected the sooner it can be treated and the greater the likelihood of recovery. Treatment is the start of the healing journey which for many can lead back to full, productive lives.

In March of this year, the provincial government announced $1.5 million in one-time funding to the St. Paul’s Hospital Foundation to explore ways to better address both hepatitis B and C epidemics in BC. In collaboration with the foundation, we’ll be talking with interested individuals and organizations from across BC, including healthcare providers, liver specialists, regional health authorities and the new First Nations’ health authority, community groups, and non-government organizations to develop options  for improving the provincial response to viral hepatitis. 

It is important that health professionals continue to emphasize that people need to be tested for hepatitis B and C so that those diagnosed can be engaged in care and treatment.

Work at the BC Centre for Excellence in HIV/AIDS has taught us some very important lessons. For HIV, “treatment as prevention” improves the health of those already infected with HIV, while simultaneously reducing the risk of HIV transmission others. This model can be adopted for hepatitis.

Applied to hepatitis C this approach could simultaneously prevent liver disease and avert further transmission of the disease, multiplying the beneficial impact of treatment.

In order to stem the hepatitis virus in BC we need to unite the voices of affected communities, health professionals, and community leaders, and transform knowledge into action.


Dr. Mel Krajden is the medical head, Hepatitis, BCCDC.  Dr. Julio Montaner is the director of the BC Centre for Excellence in HIV/AIDS.
Media Contacts:
Patrick Blennerhassett
Provincial Health Services Authority
Media pager: 604-871-5699

Kevin Hollett
BC Centre for Excellence in HIV/AIDS
Phone: 604-682-2344 ext. 66536
Mobile: 778-848-3420


World Hepatitis Day Statement

News Release

July 26, 2013

Contact: HHS Press Office
(202) 690-6343

World Hepatitis Day Statement

by HHS Secretary Kathleen Sebelius and HHS Assistant Secretary for Health Dr. Howard Koh

On World Hepatitis Day, we reaffirm our commitment to combating the “silent epidemic” of viral hepatitis.

Globally, one in 12 people has chronic hepatitis B or C infection. About 1 million people die each year from chronic viral hepatitis. Viral hepatitis is the leading cause of liver cancer in the United States and worldwide. And while it is the most common blood-borne infection and a leading infectious cause of death, claiming the lives of some 15,000 Americans each year, viral hepatitis often remains unrecognized as a public health priority.

Thanks to advances in science and policy, we have made progress with combating this silent epidemic. Hepatitis B and C are both preventable – there is a vaccine for hepatitis B and effective treatments. Hepatitis C is curable for many people, and, with the rapidly improving treatment landscape, we have hope for a higher cure rate in the near future.

The Department of Health and Human Services (HHS) recently announced it will renew its landmark Viral Hepatitis Action Plan for 2014-2016 to strengthen existing strategies to prevent new cases. The new plan will help ensure that people who are already infected receive testing and linkage to care and treatment. The Affordable Care Act, by requiring health plans to offer certain free preventive services, also provides tremendous opportunities to expand access to viral hepatitis testing, care, and treatment services.

Early detection and treatment of chronic hepatitis B and C can reduce disease progression, limit transmission to others, and prevent serious liver disease. The Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommend that adults born between 1945 and 1965 be tested for Hepatitis C.

Talk with your doctor about whether you should be tested for hepatitis B or C. You can also take an online risk assessment at http://www.cdc.gov/hepatitis/riskassessment.

Don’t let hepatitis be a silent killer any longer.


Note: All HHS news releases, fact sheets and other press materials are available at http://www.hhs.gov/news.

Like HHS on Facebook, follow HHS on Twitter @HHSgov, and sign up for HHS Email Updates.

Follow HHS Secretary Kathleen Sebelius on Twitter @Sebelius .

Last revised: July 26, 2013


Futility, discontinuation of HCV therapy more common in practice than clinical trials

Provided by Healio

Belperio PS. Clin Gastroenterol Hepatol. 2013;11:1021-1027.

July 26, 2013

Patients with hepatitis C treated with direct-acting antivirals in routine practice were more likely to experience early discontinuation or futility than those treated in clinical trials in a recent study.

Researchers evaluated data from veterans with chronic HCV genotype 1 treated with pegylated interferon and ribavirin with either boceprevir (n=661) or telaprevir (n=198) before January 2012. Patient data was collected from the Veterans Affairs’ Clinical Case Registry. HCV RNA levels were measured at 4, 8, 12 and 24 weeks of treatment.

Among treatment-naive, noncirrhotic participants, more patients in the boceprevir group had undetectable HCV RNA levels at 24 weeks (74% of cases vs. 60% of telaprevir recipients; P=.03). Early response occurred at similar rates among prior null or partial responders, relapsers and cirrhotic patients, though undetectable RNA at 24 weeks was more common among treatment-naive patients in the boceprevir group (71% vs. 58%; P=.02).

At 24 weeks, treatment discontinuation and futility had occurred in 30% and 14%, respectively, of the boceprevir group and 34% and 17%, respectively, of the telaprevir group. Multivariate analysis indicated that prior null response (OR=2.98; 95% CI, 1.73-5.13) and diabetes (OR=1.49; 95% CI, 1.01-2.21) were predictive of treatment failure among boceprevir recipients. In the telaprevir group, diabetes was predictive of failure (OR=2.15; 95% CI, 1.11-4.17) and prior relapse was associated with reduced failure risk (OR=0.18; 95% CI, 0.06-0.57).

“In routine medical practice, treatment with boceprevir- or telaprevir-based antiviral therapy had better early results than previously observed with pegylated interferon/ribavirin alone, but results [were] not quite as good as seen in the clinical trials,” researcher Lisa I. Backus, MD, PhD, national clinical manager of clinical case registries for the Office of Public Health/Population Health in Palo Alto, Calif., told Healio.com. “In particular, in routine medical practice, more patients discontinue treatment early than in clinical trials.” She said the lower early response rates observed among prior null responders suggest a need for patients and providers to make very considered treatment decisions.

Disclosure: The researchers report no relevant financial disclosures.


At the Forefront of Hepatitis Testing, Abbott Recognizes World Hepatitis Day


With ongoing advances in hepatitis diagnosis and monitoring, Abbott has been a leader in developing and improving tests for hepatitis for more than 40 years. On July 28 - World Hepatitis Day - Abbott joins with organizations around the world to help increase awareness of viral hepatitis and related diseases.

According to the World Health Organization (WHO), more than 390 million people are living with chronic hepatitis.Of those, an estimated 150 million people are chronically infected with hepatitis C, a virus transmitted through contact with the blood of an infected person.1 Unfortunately, because approximately 80 percent of people do not exhibit any symptoms following initial infection, many people with hepatitis C virus (HCV) do not know they are infected.2 If left untreated, HCV can result in serious long-term health problems such as liver damage and cirrhosis; it is also a leading cause of liver cancer.3 The good news is that with early detection and treatment, hepatitis C can be completely cured.

For decades, Abbott has worked to develop products to detect and manage hepatitis. In addition to our comprehensive array of tests for hepatitis A and B, today Abbott offers the following tests to diagnose and monitor the hepatitis C virus across the spectrum of patient care:

  • The ABBOTT PRISM HCV test is used in the blood screening environment and helps prevent the transmission of hepatitis C virus to recipients of blood, blood products, tissue and organs.
  • The ARCHITECT Anti-HCV test helps doctors diagnose hepatitis C by detecting antibodies to the virus in people with signs and symptoms of infection as well as in people who may be at risk for hepatitis C.
  • Once a person is diagnosed with hepatitis C, Abbott’s RealTime HCV Genotype II test, the first and currently only FDA-approved hepatitis C genotyping test, helps physicians find out what type or strain of hepatitis C is present. This enables physicians to create the most effective course of treatment for each patient.
  • Throughout treatment, Abbott’s RealTime HCV-Viral Load test is an important tool for monitoring the amount of virus in a patient’s blood and helps physicians understand if the patient is responding to antiviral therapy.

For people infected with hepatitis C, the World Health Organization recommends4:

  • Education and counseling options for care and treatment;
  • Immunization with the hepatitis A and B vaccines to prevent coinfection from these hepatitis viruses to protect their liver;
  • Early and appropriate medical management including antiviral therapy if appropriate; and
  • Regular monitoring for early diagnosis of chronic liver disease.

For more information:

  • Click here to learn more about hepatitis C, testing for the disease, and who is at risk [infographic]
  • Click here for a video about Abbott’s commitment to hepatitis
  • Click here to read about Abbott’s recently FDA-approved hepatitis C genotyping test
  • Click here to learn about World Hepatitis Day on the World Health Organization (WHO) website


1 World Health Organization. Hepatitis C Fact Sheet, No. 164. July 2012.

2 World Health Organization. Hepatitis C Fact Sheet, No. 164. July 2012.

3 Centers for Disease Control and Prevention. Travelers’ Health, Map 3-05: Prevalence of Chronic Hepatitis C Infection. July 2011.

4 World Health Organization Hepatitis C Fact Sheet, No. 164, July 2013.