Jeanne White Ginder, Mother of Ryan White, Speaks out against Hershey School AIDS Discrimination

PRESS RELEASE

March 20, 2012, 3:17 p.m. EDT

Mother of the late Ryan White, the American teenager from Kokomo, Indiana, who, in the mid-1980s, was expelled from his Indiana middle school because he was HIV-positive, says Hershey School discrimination case, “brings back horrible memories of what Ryan had to go through.”

FT. LAUDERDALE, Fla., Mar 20, 2012 (BUSINESS WIRE) -- --On December 1st, 2011 (the 24th observation of World AIDS Day) the Hershey Trust’s Milton Hershey School was sued in federal court for rejecting an otherwise qualified 13-year-old boy due to his HIV-positive status; today--almost 22 years after her own son died--White Ginder believes the Hershey School situation offers, “...an opportunity to educate Hershey to do the right thing and lead by example.”

Jeanne White Ginder, the mother of the late Ryan White, the American teenager from Kokomo, Indiana, who, in the mid-1980s, was expelled from his Indiana middle school because he was HIV-positive, is speaking out today against a present day case of HIV/AIDS discrimination by school administrators at Pennsylvania’s prestigious Milton Hershey School--discrimination that bears a striking resemblance to the ordeal that her own son and family had to endure 27 years ago.

On December 1st, 2011 (the 24th observation of World AIDS Day) the Hershey Trust’s Milton Hershey School was sued in federal court for rejecting an otherwise qualified 13-year-old boy due to his HIV-positive status misguidedly calling him a “direct threat to the health and safety of others.”

Today--almost 22 years after her own son died of AIDS-related complications--White Ginder believes the Hershey School situation offers an important opportunity to speak out against such discrimination and to educate Hershey and the community-at-large about the wrongheadedness of such prejudice.

“This April 8th--Easter Sunday--will mark twenty-two years since my son Ryan passed away after his truly courageous battle with AIDS--and our family’s battle with the discrimination, fear-mongering and misinformation it fostered in Indiana and across America back in the earliest days of the epidemic,” said Jeanne White Ginder in a statement from Florida, where she now lives. “The news that in this day and age, the Milton Hershey School rejected an otherwise qualified 13-year-old boy due to his HIV-positive status brings back horrible memories of what Ryan had to go through twenty-seven years ago when all he wanted to do was simply to go back to school. I am truly saddened by the discrimination and ignorance shown today by administrators at the Hershey School and the three Board Members who sit on both the school and the chocolate company’s Board of Directors; however, in honor of Ryan’s indomitable spirit, I have to look at this situation as an opportunity to educate Hershey to do the right thing and lead by example. Hershey--both the school and the chocolate company--should apologize and denounce its rejection of the boy as unfounded and discriminatory and really step up to the plate to educate both their staffs and the public-at-large about the realities of HIV/AIDS.”

Shortly after news broke just before World AIDS Day 2011 about the Hershey School’s rejection of the HIV-positive boy, AIDS Healthcare Foundation (AHF) hosted a press conference in Washington, D.C., to announce the launch of a campaign against HIV/AIDS discrimination at Hershey School in Pennsylvania and in support of the federal discrimination lawsuit filed on behalf of a 13-year-old boy who was rejected for admission at Hershey explicitly due to his HIV-positive status. At the event, AHF announced it was going to contribute up to $50,000 to support a lawsuit filed by AIDS Law Project of Pennsylvania on behalf of the boy.

According to the Associated Press (claim:Hershey School Rejects HIV-Positive Pa. Boy)(claim:By Peter Jackson)(claim:12/1/11): “A private boarding school connected with the Hershey chocolate company says it was trying to protect other students when it denied admission to a Philadelphia-area teenager because he is HIV-positive. The AIDS Law Project of Pennsylvania filed a lawsuit on behalf of the unidentified boy in U.S. District Court in Philadelphia on Wednesday, claiming the Milton Hershey School for disadvantaged students violated the Americans with Disabilities Act. School officials acknowledged that the 13-year-old boy was denied admission because of his medical condition. They said they believed it was necessary to protect the health and safety of the 1,850 others enrolled in the residential institution, which serves children in pre-kindergarten to 12th grade and where students live in homes with 10 to 12 others.”

“The ignorance displayed by the Hershey School’s leadership is unacceptable and demonstrates just how much work there is still to be done to dismantle the fear and misinformation that still surrounds this disease more than 25 years after Ryan White,” said Michael Weinstein, President of AIDS Healthcare Foundation.

Ryan White was an American teenager from Kokomo, Indiana who, in the mid-1980s, was expelled from middle school because he was HIV-positive. A lengthy legal battle with the school ensued and White became a galvanizing force in educating the country about HIV & AIDS at a time when misinformation about the disease was widespread. After his death in 1990, the U.S. Congress passed a major piece of legislation named in his honor, the Ryan White CARE Act, which provides funding for HIV/AIDS programs for low-income American.

AHF has also launched a website www.EndHIVStigma.org where the public can learn more about the Hershey School case, learn the facts about HIV/AIDS and send e-letters to three Hershey Company board members who also sit on the board of the Milton Hershey School Trust.

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 135,000 individuals in 26 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. www.aidshealth.org

Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50210682&lang=en 

SOURCE: AIDS Healthcare Foundation

Source

NICE final draft "yes" for Incivo

UK News | March 20, 2012

Lynne Taylor

The National Institute for Health and Clinical Excellence (NICE) has issued final draft guidance recommending Janssen Cilag's Incivo (telaprevir), in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease.

The final guidance recommends the drug as an option for the treatment of such patients who are previously untreated or in whom previous treatment with peginteron alfa and ribavirin has failed, including people whose condition has relapsed, partially responded or did not respond.

Commenting on the draft recommendations, Meindert Boysen, programme director for technology appraisals at NICE, pointed out that chronic hepatitis C can have a significant impact on quality of life, particularly if it progresses to the fibrosis and cirrhosis stages.

"Fear of transmitting the disease is also a concern, particularly for women of child-bearing age for whom there is a risk of transmitting the disease to their unborn child,” he added.

NICE says its independent appraisal committee had heard that the current treatment regimen for chronic hepatitis C is often lengthy and that the side effects of treatment themselves can have a significant impact on daily life.

"The significant improvement in sustained virological response rates seen with telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone, and its potential for shortening the treatment time from the full 48-week course needed for a virological response, therefore represents a major benefit for people with chronic hepatitis C," said Mr Boysen.

NICE is “pleased to be able to recommend teleprevir as a cost-effective use of NHS resources" alongside the final draft guidance also issued this month for Merck Sharp & Dohme's Victrelis (boceprevir), he added.

This latter final draft also recommends Victrelis, in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease.

Graham Foster, professor of hepatology at Barts and the London School of Medicine and Dentistry, welcomed NICE’s positive recommendation for Incivo’s clinical and cost-effectiveness. "We have approved new treatments which significantly increase these patients' chances of clearing the virus and offers some patients a shorter treatment duration. We must now ensure that patients are in a position to access the new antiviral treatments which offer them a very good chance of clearing the virus,” said Prof Foster.

- Figures from 2009 suggest that around 146,000 people were chronically infected with the hepatitis C virus. Genotype 1 is the most common subtype of hepatitis C in England and Wales, affecting 40%-50% of people with hepatitis, and is the most resistant to treatment. Poor diagnosis and compliance rates and a high annual incidence of new infection mean that chronic hepatitis C presents a major public health challenge, despite the availability of treatments that provide the opportunity to address this challenge, says NICE.

Source

Discovery provides blueprint for new drugs that can inhibit hepatitis C virus

March 19, 2012 in Medical research

Chemists at the University of California, San Diego have produced the first high resolution structure of a molecule that when attached to the genetic material of the hepatitis C virus prevents it from reproducing.

Hepatitis C is a chronic infectious disease that affects some 170 million people worldwide and causes chronic liver disease and liver cancer. According to the Centers for Disease Control and Prevention, hepatitis C now kills more Americans each year than HIV.

The structure of the molecule, which was published in a paper in this week's early online edition of the journal Proceedings of the National Academy of Sciences, provides a detailed blueprint for the design of drugs that can inhibit the replication of the hepatitis C virus, which proliferates by hijacking the cellular machinery in humans to manufacture duplicate viral particles.

Finding a way to stop that process could effectively treat viral infections of hepatitis C, for which no vaccine is currently available. But until now scientists have identified few inhibiting compounds that directly act on the virus's ribonucleic acid (RNA) genome—the organism's full complement of genetic material.

"This lack of detailed information on how inhibitors lock onto the viral genome target has hampered the development of better drugs," said Thomas Hermann, an associate professor of chemistry and biochemistry at UC San Diego who headed the research team, which also included scientists from San Diego State University. The team detailed the structure of a molecule that induces the viral RNA to open up a portion of its hinge-like structure and encapsulate the inhibitor like a perfectly fit glove, blocking the ability of the hepatitis C virus to replicate.

The molecule is from a class of compounds called benzimidazoles, known to stop the production of viral proteins in infected human cells. Its three-dimensional atomic structure was determined by X-ray crystallography, a method of mapping the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread. The angles and intensities of the light beams allowed the scientists to calculate the structure of the viral RNA-inhibitor complex.

"This structure will guide approaches to rationally design better drug candidates and improve the known benzimidazole inhibitors," said Hermann. "Also, the crystal structure demonstrates that the binding pocket for the inhibitors in the hepatitis C virus RNA resembles drug-binding pockets in proteins. This is important to help overcome the notion that RNA targets are so unlike traditional protein targets that drug discovery approaches with small molecule inhibitors are difficult to achieve for RNA."

Provided by University of California - San Diego (news : web)

Source

877-HELP-4-HEP; a Peer Advocacy Success Story

San Francisco, CA, March 19, 2012 --(PR.com)-- The first week of February brought both good news and bad news to Mary*. She learned that her husband was an early responder to the powerful triple drug cocktail for hepatitis C. She also found out that their family’s state-sponsored health insurance coverage was going to be terminated.

Several months ago, Mary had called 877-HELP-4-HEP (877-435-7443). Many conversations with peer counselors helped her husband prepare to start treatment at the beginning of the year and provided much needed emotional support for the family.

One counseling conversation raised a flag. A few short weeks after her husband started treatment; Mary mentioned that she got a part-time job to help buy groceries for their family of five. Her HELP-4-HEP counselor was on the alert. What Mary did not consider was that her extra wages might alter her family eligibility for state-sponsored insurance at a very inopportune time.

Mary’s counseling team began reviewing options to avoid disruptions to treatment. When her “bad news” came, it was met with an action plan. Mary’s husband will continue under the care of his current treating physician, receive medications at no cost through patient assistance programs, and get the tests necessary to monitor his progress at a discount.

“This story could have had another ending. It was the proactive work of a group of HELP-4-HEP counselors who made the difference for this family,” said peer counselor, Sue Simon from Hepatitis C Association.

HELP-4-HEP is a project of The Support Partnership which includes HealthPro (formerly Hep-C ALERT), FL; Hepatitis C Association, NJ; Hepatitis Education Project, WA; Hep C Connection, CO; and Project Inform, CA. The helpline operates Monday through Friday, 9:00am to 7:00pm EST. To learn more, visit www.help4hep.org  or email info@help4hep.org.

877-HELP-4-HEP peer counselors are available to help your patients too. Palm cards are now available to distribute. Please email your organization’s contact name, site name, address, phone number, and the number of cards desired.

* Name changed.

Contact Information

The Support Partnership
Andi Thomas
954-692-0450
Contact
www.help4hep.org
Denny Simon
908-812-2488

Source

Hep C Death Rates Steadily Increase

Monday, March 19, 2012

Researchers recently uncovered some startling news concerning hepatitis C: death rates from the virus gradually increased from 1999 to 2007 and now exceed HIV-related deaths in the United States.

The study, primarily funded by the Centers for Disease Control and Prevention, was recently published in the Annals of Internal Medicine.

According to the study, an estimated 3.2 million people in this country are infected with chronic hepatitis C virus. At least half of those infected may not even know it.

Researchers analyzed death records for 22 million people from 1999 to 2007 to examine mortality rates for hepatitis B, hepatitis C and HIV (to use for comparison). They found that over the course of eight years, annual deaths from hepatitis C increased (15,106 in 2007), while those from HIV decreased (12,734 in 2007).

Baby boomers seem to be affected the most. One in every 33 is infected with the virus.

The current screening guidelines from the CDC only recommend testing people known to be at high risk. Now the agency is debating whether to change those guidelines to encourage anyone born between 1945 and 1965 to get a one-time screening. The one-time screening, according to the CDC, has the potential to save 82,000 lives.

For more information about the study, visit www.annals.org.

Source

Potential First-in-Class Hepatitis C Vaccine Enters Phase I/II Trials

POSTED: MARCH 19, 2012

by George Ochoa

A preventive vaccine against hepatitis C virus (HCV) that would potentially be the first in that class is entering a Phase I/II clinical trial, according to the Basel, Switzerland-based biopharmaceutical company Okairos.

This is the first multicenter, double-blinded, randomized, placebo-controlled trial of a vaccine to prevent HCV infection, the company stated. The trial, born of collaboration between Okairos and the National Institute of Allergy and Infectious Diseases, will be conducted by co-principal investigators from Johns Hopkins University and the University of California, San Francisco.

The Phase I/II trial follows promising Phase I results published in January in Science Translational Medicine (Barnes et al. 2012;4:115ra1). In that study in healthy volunteers, the T-cell–based preventive vaccine was safe and well tolerated, and, the authors reported, it was shown possible “to generate very strong, broad, long-lasting, and functional T-cell responses against HCV in healthy donors using an adenovirus-based approach.” The Phase I/II trial will test the vaccine’s potential effectiveness in protecting against chronic HCV infection.

Enrolling 350 subjects, the trial will begin with an interim Phase I analysis of safety and immunogenicity data in a subset of the participants. The study’s primary endpoints will measure the incidence of chronic HCV infection, and the vaccine’s safety and tolerability.

Okairos’ HCV vaccine is based on a technology platform that uses proprietary, chimpanzee-derived adenovirus vectors to stimulate a robust T-cell response against selected antigens. Okairos plans to develop other T-cell vaccines against infectious diseases for which there are currently no effective vaccines, and to pursue therapeutic vaccines to treat cancer.

—Based on an Okairos press release and the article in Science Translational Medicine

Source

Also See: Okairos Announces Initiation of Phase I/II Clinical Trial for Potential First-in-Class Hepatitis C Vaccine

Antiviral strategies in hepatitis C virus infection

Journal of Hepatology
Volume 56, Supplement 1 , Pages S88-S100, 2012

Christoph Sarrazin, Christophe Hézode, Stefan Zeuzem, Jean-Michel Pawlotsk

Abstract

Summary

Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. Sustained virological response rates in the range of 6675% and 5966% (2988% if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found.

Source

The Faces of Hepatitis C

The Faces of Hepatitis C

You are a doctor or a nurse--You are a fifth grade grade teacher

Your skin is white or brown or black--you are Mecxican or Asian, Caucasian,or African American

You are very old, have grandchildren,near the end of your golden years

You are middle-aged--children grown and gone-ready to "enjoy" your life --

You are a young mother with a small child-a young father trying to provide for his family--

You are a teenager--waiting for proms,boy or girlfriends, your first kiss dreaming of college and a car of your own--

You are a newborn lying in your mother's arms

YOU are the Faces of Hepatitis C

I may not recognize you as you pass me on the street or in the store where I shop or the church where I worship, but you are there

The Faces of Hepatitis C

My heart cries out for you,for what fate has given you--it was not your fault--it was just meant to be

My heart swells with pride for you--your courage,your faith—you have been asked to keep going when others would have given up

You wait anxiously for another loving person to give you the "The Gift of Life"

The gift of their own liver at the end of THEIR life. I am filled with love for each of you--my brother--my sister and those I have met and those I will never know--

You see--I am one of those faces

The faces of Hepatitis

Given by God...written by Selles Dole

Selles lost her battle with HCV November 29, 2008

May You Always Sleep In The Arms Of Angels

The horizon: New targets and new agents†

Clinical Liver Disease

Volume 1, Issue 1, pages 24–27, February 2012

Review

Alison B. Jazwinski M.D., M.H.S., Andrew J. Muir M.D., M.H.S.^‡,*

Article first published online: 6 MAR 2012

DOI: 10.1002/cld.2

Copyright © 2012 the American Association for the Study of Liver Diseases

Abstract

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DAA, direct-acting antiviral; HCV, hepatitis C virus; ILLUMINATE, Illustrating the Effects of Combination Therapy With Telaprevir; NI, nucleoside inhibitor; NNI, nonnucleoside inhibitor; NS, nonstructural; PEG-IFNα, pegylated interferon-α; PI, protease inhibitor; RBV, ribavirin; RESPOND-2, Retreatment With HCV Serine Protease Inhibitor Boceprevir and Peginterferon/Rebetol 2; RGT, response-guided therapy; SPRINT-2, Serine Protease Inhibitor Therapy 2; SVR, sustained virological response.

Patients infected with hepatitis C virus (HCV) and their physicians have long been awaiting a more tolerable and effective treatment regimen. New agents are currently in development that directly target the HCV life cycle [direct-acting antivirals (DAAs)]. This review discusses these agents and the targets of therapy.

New Targets of Therapy

The HCV viral life cycle is shown in Fig. 1. The HCV structure encodes 10 viral proteins: 4 structural proteins and 6 nonstructural proteins (Table 1). The nonstructural proteins, particularly nonstructural 3/4A (NS3/4A), NS5A, and NS5B, compose the majority of the targets for the new DAA medications.1

Figure 1. Viral life cycle. HCV enters the cell by receptor-mediated endocytosis. Positive-strand RNA is released into the cytoplasm, and then it is translated into a polyprotein. Polyprotein processing occurs: the bonds between the proteins are cleaved, and this results in four structural proteins and six nonstructural proteins. Viral replication occurs through the creation of negative-strand RNA, which serves as a template for the production of positive-strand RNA; that RNA is then packaged and released from the cell.

(Click table to enlarge)

NS3/4A

NS3/4A protease inhibitors (PIs) are the furthest along in drug development and include telaprevir and boceprevir, which have been approved for clinical use. NS3/4A PIs have high antiviral efficacy against genotypes 1 and 2 but not against genotype 3.2

NS3/4A inhibitors have a low genetic barrier to resistance; resistant strains develop quickly and prevent viral eradication with monotherapy.3, 4 HCV subtype 1a develops resistant strains to telaprevir more quickly than subtype 1b. One nucleotide change is required for subtype 1a to change the amino acid and form a resistant strain, whereas two nucleotide changes are required for subtype 1b (Fig. 2).5

Figure 2. Telaprevir resistance. One common location for the development of strains resistant to telaprevir is position 155. In patients with genotype 1a, the nucleotide sequence is AGA, which codes for arginine. Only one nucleotide change is required to result in the AAA sequence, which codes for lysine. This is in contrast to genotype 1b: two nucleotide changes are required for the AAA sequence and the change to lysine.

NS5B

Two categories of NS5B RNA polymerase inhibitors are in development: nucleoside inhibitors (NIs) and nonnucleoside inhibitors (NNIs). NIs mimic the natural substrates, are incorporated into the growing RNA chain, and cause termination of replication.6 NNIs bind to distant sites on the enzyme and cause a conformational change, which renders the polymerase ineffective.6, 7

There is a high genetic barrier to resistance with polymerase inhibitors and particularly with NIs because the active site of NS5B is highly conserved and amino acid substitutions at every position of the active site can result in a loss of function.8 Because NNIs bind to sites distant from the active center, resistance develops more frequently. Similarly, NIs have antiviral activity against all HCV genotypes because the active site of NS5B is conserved; however, NNIs have a more limited spectrum of activity.9

Other

The NS5A viral protein and cyclophilin A host protein are also important components of the viral replication complex (Fig. 3), and agents that target these proteins, which have been termed replicase-binding inhibitors, are also in development.3 The exact mechanism by which these proteins participate in viral replication is currently under investigation, although early trials with inhibitors of these proteins have shown robust antiviral activity.10, 11

Figure 3. Replication complex. The viral nonstructural proteins, in addition to host proteins such as cyclophilin A, make up the replication complex and are the targets of the new DAA therapy. The exact roles of many of these proteins are still being elucidated, although inhibitors directed at them have potent antiviral activity.

Current Practice and Future Directions

At the present time, because of the relatively high efficacy of treatment, patients infected with genotypes 2 and 3 receive 24 weeks of treatment with pegylated interferon-α (PEG-IFNα)/ribavirin (RBV).12 However, the side effects and the duration of treatment remain limitations, and DAAs are in development that will treat patients infected with genotypes 2 and 3.

The standard-of-care treatment for patients with genotype 1 infections now includes the use of telaprevir or boceprevir in combination with PEG-IFNα/RBV. Overall, the additions of telaprevir and boceprevir have improved the rates of response, but the significant side effects and the duration of treatment remain problems.13–17 Additionally, there are certain subgroups of patients who do not benefit from the addition of telaprevir or boceprevir to PEG-IFNα/RBV. Tables 2 and 3 and Fig. 4 show the results of phase 3 trials and highlight those groups that continue to have suboptimal response rates with triple therapy.13–17

Figure 4. SVR rates according to the fibrosis score in the REALIZE study. SVR indicates a negative viral load 24 weeks after the completion of therapy. The REALIZE study evaluated the efficacy of telaprevir in prior treatment relapsers, partial responders, and null responders. The results came from subgroup analyses.

(Click table to enlarge)

Abbreviations: ILLUMINATE, Illustrating the Effects of Combination Therapy With Telaprevir; RGT, response-guided therapy; SPRINT-2, Serine Protease Inhibitor Therapy 2.

* SVR indicates a negative viral load 24 weeks after the completion of therapy.

† In the ADVANCE trial of telaprevir,13 the T12PR group received telaprevir plus PR for 12 weeks and then PR alone for 12 weeks if HCV RNA results were negative at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point. The T8PR group received telaprevir plus PR for 8 weeks, then a placebo plus PR for 4 weeks, and finally PR for 12 or 36 weeks (depending on the HCV RNA levels at weeks 4 and 12).

‡ In the ILLUMINATE trial of telaprevir,15 all patients received 12 weeks of telaprevir plus PR. The HCV RNA level was assessed at weeks 4 and 12. If HCV RNA results were negative at weeks 4 and 12, patients were randomized into two groups: the T12PR24 group, which received another 4 weeks of therapy, and the T12PR48 group, which received another 28 weeks of therapy. Patients who did not achieve negative HCV RNA results at weeks 4 and 12 received 28 additional weeks of PR (i.e., the T12PR48 RGT group).

§ In the SPRINT-2 trial of boceprevir,16 the RGT group received PR for 4 weeks and then boceprevir for 24 weeks plus PR for 28 weeks. If patients had negative HCV RNA results at weeks 8 and 24, they stopped therapy at 28 weeks; if patients had detectable HCV RNA, they continued for another 20 weeks. The BPR48 group received lead-in PR for 4 weeks and then boceprevir plus PR for 44 weeks.

(Click to enlarge table)

Abbreviations: RESPOND-2, Retreatment With HCV Serine Protease Inhibitor Boceprevir and Peginterferon/Rebetol 2; RGT, response-guided therapy.

* SVR indicates a negative viral load 24 weeks after the completion of therapy.

† In the REALIZE trial of telaprevir,14 the T12PR48 group received telaprevir plus PR for 12 weeks and then PR for 36 weeks. The Li-T12PR48 group received PR for 4 weeks, then telaprevir plus PR for 12 weeks, and finally PR for 32 weeks.

‡ In the RESPOND-2 trial of boceprevir,17 the RGT group received PR for 4 weeks and then boceprevir plus PR for 32 weeks. Patients with negative HCV RNA results at weeks 8 and 20 stopped treatment at week 36; patients with detectable HCV RNA received therapy for another 12 weeks. The BPR48 group received lead-in PR for 4 weeks and then boceprevir plus PR for 44 weeks.

§ Not studied.

Generally, interferon-α is the drug that limits tolerability in the majority of patients. Thus, future regimens are being developed first to minimize interferon-α exposure and then ideally to avoid it entirely. Phase 3 trials of PIs have demonstrated that patients who achieve an extended rapid virological response can receive a shortened course of therapy (24 weeks with telaprevir and 28 weeks with boceprevir) with similar overall response rates. Thus, PIs may be considered the first interferon-α–sparing therapy.

The use of multiple DAAs is currently being studied with the goal of developing interferon-α–sparing and interferon-α–free regimens. Figure 5 shows the various combinations of therapy that are currently being studied both with and without PEG-IFNα and RBV.18 Over the next 5 to 10 years, as we work to develop an effective interferon-free regimen, there will be ongoing research to determine the shortest duration of interferon-α–sparing therapy possible. Quadruple-therapy regimens are likely the next step in this process.

Figure 5. Combinations of DAAs currently under study. Trials are being conducted that include regimens of quadruple therapy (2 DAAs plus PEG-IFNα/RBV) as well as regimens using RBV but not PEG-IFNα and regimens using only DAAs.

Evidence showing that a sustained virological response (SVR) can be achieved with the use of DAAs and without the concurrent use of PEG-IFNα and RBV has been published recently.19 Patients with genotype 1 and a prior treatment null response were treated with an NS5A replication complex inhibitor (Daclatasvir) and an NS3 PI (Asunaprevir) alone or in combination with PEG-IFNα/RBV. All patients who received the quadruple therapy achieved SVR by 12 weeks, and 4 of 11 patients who received the all-oral regimen achieved SVR by 12 weeks. These results provide proof of concept that quadruple therapy offers hope of cure to previous null responders and that treatment regimens that do not include interferon-α are possible and likely. Many of the treatment regimens under investigation still include RBV; this is due to evidence from phase two studies of PIs showing that the use of RBV decreases viral breakthrough and relapse.20

Many of the treatment regimens under investigation still include RBV; this is due to evidence from phase two studies of PIs showing that the use of RBV decreases viral breakthrough and relapse.20

Personalized Treatment Regimens

HCV is leading the field of personalized medicine. Depending on a patient's history of treatment, degree of fibrosis, and race, a potential future treatment strategy involves the separation of patients into those with a favorable response profile and those with an unfavorable response profile and then the choice of an appropriate treatment regimen. Patients who have a favorable response profile will more frequently respond to the triple-therapy regimens that are currently available and may be the ones who will do well with the early interferon-free regimens. Patients who have an unfavorable response profile may experience improved response rates with upcoming quadruple therapy while additional interferon-α–sparing and interferon-α–free regimens are in development. Another potential future treatment algorithm may include the upfront treatment of patients with combination DAA therapy and, if the treatment fails, the initiation of a regimen that also includes PEG-IFNα/RBV (Fig. 6).

Figure 6. Potential future treatment strategies.

In conclusion, the development of new antiviral agents is currently underway with the ultimate goal of using DAAs to target multiple viral and host proteins to increase antiviral efficacy, prevent resistance, and improve the side effect profile of HCV treatment.

References

Source

Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNA load

Journal of Hepatology
Volume 56, Issue 4 , Pages 788-794, April 2012

Karin Neukam, Angela Camacho, Antonio Caruz, Norma Rallón, Almudena Torres-Cornejo,Jürgen K. Rockstroh, Juan Macías, Antonio Rivero, José M. Benito, Luis F. López-Cortés,Jacob Nattermann Jesús, Gómez-Mateos Vicente Soriano, Juan A. Pineda

Received 8 August 2011; received in revised form 2 November 2011; accepted 17 November 2011. published online 14 December 2011.

Abstract

Background & Aims

This study aimed at developing a predictive algorithm based on interleukin 28B (IL28B) genotype, hepatitis C virus (HCV) genotype, and plasma HCV-RNA load, which could accurately allow us to define the probability of response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in HIV/HCV-coinfected patients.

Methods

Five hundred and twenty-one treatment-naive HIV-infected patients, who initiated HCV therapy with Peg-IFN/RBV, were analysed in an on-treatment basis. Patients were categorized as unlikely responders, uncertain responders, and anticipated responders (<20%, 20–60%, and >60% probability to achieve SVR, respectively).

Results

HCV genotype, baseline HCV-RNA load, and IL28B genotype were confirmed as independent predictors of SVR in a logistic regression analysis. A stepwise algorithm based on these three variables was created based on 321 patients and evaluated in the remaining 200 patients. Unlikely responders included patients with genotype 1 or 4, HCV-RNA load greater than or equal to 600,000 IU/ml, and rs12979860 non-CC (rate of SVR: 17.3%). Anticipated responders were those with HCV genotype 2–3, patients harboring HCV genotype 4 and IL28B CC, as well as those who simultaneously bore HCV genotype 1, HCV-RNA load <600,000 IU/ml, and IL28B CC (rate of SVR 74.1%, 77.8%, and 64.4%, respectively). The area under the receiver operating characteristic curve of the model was 0.77 (0.733–0.814).

Conclusions

The combined use of IL28B genotype, HCV genotype, and HCV-RNA load enables to easily identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients, until more effective options are available, at least if they do not show advanced liver fibrosis.

Source

City hitting hepatitis C

By CARL CAMPANILE

Last Updated: 1:41 AM, March 17, 2012

Posted: 1:41 AM, March 17, 2012

The Bloomberg administration is launching a campaign to prevent the spread of the deadly hepatitis C virus, The Post has learned.

The Check Hep C initiative targets high-risk populations in Harlem, the South Bronx, central Brooklyn and parts of Staten Island and Queens.

At-risk populations include drug users who have shared infected needles, people infected with HIV and immigrants from countries with high hepatitis prevalence, including Egypt, Pakistan and the former Soviet Union.

Hepatitis C, when undetected, can cause fatal liver disease.

The city Health Department will award up to $1.3 million in contracts to community-based medical clinics that would provide free counseling and hepatitis C testing.

Patients will also be given a “health coach” to help navigate the medical system. And there will be a community-awareness campaign to reach those at risk.

The Fund for Public Health, the fund-raising arm of the Health Department, is providing financing for the project.

ccampanile@nypost.com

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Systemic Treatment of Liver Cancer

Hepatocellular carcinoma LSF inhibition via FQI1

By: Travis Giddings

Published: Mar 16, 2012 10:28 am Reviewed By: Joseph V. Madia, MD

(dailyRx)

While no systemic treatment currently exists for liver cancer (hepatocellular carcinoma), a series of experiments in rats has identified viable target worthy of further investigation.

A gene called LSF (Late SV40 Factor) may be a target in liver cancer that drugs could be developed to target and wipe out.

Every cancer has a series of common mutations that predispose the transformation from normal cell to cancer. These genes are called oncogenes. Some cancers have a unique profile with specific oncogenes for that cancer, or may share similar mutations with other, closely related cancers.

In the search for a systemic treatment for liver cancer, the LSF gene has been shown in previous studies to appear specifically in hepatocellular carcinoma.

LSF, like many oncogenes, regulates cellular growth. After completing their laboratory experiments and transplating human cancers into rats, researchers concluded that LSF inhibition is worthy of further study and remains a promising drug target.

Boston University researchers began testing 20 compounds of isoquinolinones, with one candidate quickly outperforming the others.

Factor Quinolinone Inhibitor 1 (FQI1) is the lead candidate for further study, and was proven to inhibit DNA replication of LSF in studies performed both in a laboratory setting and inside the cell.

Most notably, FQI1 increased cellular death in cancer, but did not affect normal cells.

Supplementary information provided by the publication of the study extensively documents the methods used by the team to make the isoquinolinones compounds referenced.

Research was published in the journal Proceedings of the National Academy of Sciences of the United States of America.

The authors of the study declared that there was no financial conflict of interest in the publication of their research.

Liver Cancer (Hepatocellular Carcinoma)

The American Cancer Society estimates that there are over 26,000 new cases of primary liver cancer and bile duct cancer in the United States each year, and they are responsible for over 19,000 deaths. The average man has about a 1% chance of developing this cancer over his lifetime, while the average woman has about a half percent chance.

Primary liver cancer most commonly includes hepatocellular carcinoma (HCC) and can coexist with cholangiocarcinoma, a cancer of the bile ducts between the liver and gall bladder. It is important to note that most cases of cancer in the liver are metastases from other cancers, such as those from the colon, breast, or prostate. Primary liver cancers begin in the liver itself. Other less common forms of primary liver cancer include angiosarcomas and hemangiosarcomas (cancers that begin in the blood vessels of the liver), lymphoma of the liver, and hepatoblastoma (a rare pediatric cancer usually occurring in children under three years of age). There are also several variants of benign liver tumors. Hepatocellular adenomas (a benign liver tumor associated with oral contraceptive use and glycogen storage disease) must be watched closely, as they have a potential to turn cancerous.

Hepatocellular carcinoma, the most common form of liver cancer, is strongly associated with infection by chronic hepatitis B and C. These infections cause liver cancer more often in Asian and African countries where hepatitis viruses are endemic and people acquire the disease early in their life.

Cases of liver cancer in the United States have tripled over the past three decades. While the most common cause of liver cancer used to be from alcohol abuse and the resulting cirrhosis of the liver, hepatitis C infection is now a leading cause. Obesity, particularly fatty liver disease, is also implicated. Other causes include hemochromatosis (a disease that causes the body to store too much iron), high exposure to aflatoxins (a mold found in peanuts, rice, soybeans and corn; rare in developed countries), and Type 2 diabetes.

Symptoms of HCC usually present with classic signs of liver dysfunction such as jaundice (yellowing of the skin due to too much bilirubin), bruising and blood clotting problems (due to the liver making the clotting factors in our blood), and ascites (fluid buildup in the abdomen from liver dysfunction). Other general symptoms include nausea, fatigue, vomiting, and unintentional weight loss.

In patients who are at high risk for HCC, screening is usually done with ultrasound and CT scan, as well as MRI. While there is no reliable blood test for liver cancer screening, a high level of alpha-fetoprotein (AFP) should be considered suspicious for liver cancer. Liver biopsy is also done, although this is not necessary for diagnosis if imaging is definitive.

Treatment for HCC is difficult, as many patients with liver cancer also have damaged livers from cirrhosis. Treatment must be balanced between treating the cancer and also mitigating the risk of liver failure. Early stage cancer has the potential for surgical removal, however most cases of liver cancer are discovered when they are advanced, making surgery difficult. Other treatments are dependent on the size and location of the tumors, such as ethanol injection into the tumor (small tumors), radiofrequency ablation (using high-frequency radiowaves to destroy the tumor), transcatheter arterial chemoembolization (cuts off the blood supply to unresectable tumors), and cryosurgery (destroying cancerous tissue with subzero temperatures). Liver transplantation is a relatively successful option for patients without metastatic spread. Sorafenib (marketed as Nexavar) is a tyrosine kinase inhibitor that has shown efficacy in treating HCC.

Ultimately, HCC is a difficult cancer to treat and survival rates are low, with most cancers being unable to be completely removed. These patients usually succumb to the disease within three to six months. Across the board, patients with a solitary small tumor of less than three centimeters in size have a five-year survival rate of 20%. Patients with advanced disease have a one-year survival rate of 30%.

Prevention of liver cancer is extremely effective if vaccinated against hepatitis B. Avoidance of alcohol abuse is also effective. Other patients with different causes of cirrhosis or chronic liver inflammation will benefit from routine ultrasound screening and AFP measurements in the hope of detecting cancer early.

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Health Watch: Developments emerge in treating hepatitis C

3:09 PM, Mar. 16, 2012

Written by Dr. Carl West

Hepatitis C is a form of chronic liver disease that results in 8,000 to 10,000 deaths in the United States each year. People suffering complications from hepatitis C can develop jaundice, internal bleeding, malnutrition, and kidney damage. Hepatitis C is the leading cause of liver failure, for which the only viable treatment is liver transplantation.

Until recently, the standard treatment for hepatitis C has been only somewhat successful, curing just under 50 percent of patients. However, in 2011 the Food and Drug Administration approved two new drugs, Victrelis and Incivek. When used in conjunction with the standard treatment, these new medications have increased the cure rate for hepatitis C to about 70 percent. In addition, there are newer drugs currently being studied that appear to offer even higher levels of cure with fewer side effects. We expect these medications to be available in about three years.

» What if I was treated for hepatitis C before and I was not cured? Following FDA approval of Victrelis and Incivek, my colleagues and I called our patients with hepatitis C who were not cured after following the standard therapy and invited them to come back in for the new treatment. We've had very good success, our patients have responded well, and our cure rate reflects the national cure rate of approximately 70 percent.

» What is the new treatment protocol? The treatment protocol for hepatitis C lasts for 24 to 48 weeks and it can have some unpleasant side effects, including fatigue, skin rash, and low white-blood-cell count. The protocol requires a weekly shot of interferon and daily pills to enhance the impact of the interferon. One of the new medications is added to this standard treatment regimen and while it may increase the side effects, it can also shorten the duration of treatment.

» How do you know the treatment has been successful? As treatment progresses, we measure the virus counts by drawing blood samples. Prior to treatment, it is not unusual for the virus count of someone with hepatitis C to measure in the millions. Our goal is for the virus count to become undetectable within a few weeks of treatment and with these new drugs we are able to accomplish this in the majority of patients. It is very gratifying to see a patient's virus count go from 10 to 20 million to virtually nothing.

» What if I have already suffered liver damage from hepatitis C? Studies have shown that if patients with liver damage undergo successful therapy for hepatitis C and the virus is eliminated, the liver can partially recover from the damage. This is an important incentive for people who have undergone the standard treatment for hepatitis C with no success.

» How do people contract hepatitis C? Hepatitis C is only acquired by blood-to-blood contact. This can happen by sharing a syringe or sharing a razor blade. Nurses and doctors are at increased risk because they can get accidentally stuck with a needle while treating a patient. Rescue personnel at the scene of a bloody accident are also at higher risk if they suffer a cut in the line of duty. Blood transfusions were not screened for hepatitis C until the 1980s, so people who received transfusions prior to that time are at higher risk.

There is a widespread misconception that once you have hepatitis C there is no cure, but this is not true. The new treatment is very promising. If you have been treated for hepatitis C in the past with no success, I urge you to try again for a cure with the new drugs now available.

Dr. Carl West is board certified in gastroenterology and internal medicine. He is on the medical staff of Cayuga Medical Center and is in practice with Gastroenterology Associates of Ithaca, where he can be reached at (607) 272-5011.

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Hep C Drugmakers' Best Outcome

By Brian Orelli, PhD, The Motley Fool Posted 8:47PM 03/16/12

Treating hepatitis C is a losing proposition. Unlike treatments for chronic diseases -- high blood pressure or diabetes, for instance -- if a hepatitis C drug does its job, the patient is cured. It's a one-and-done treatment. Since the hepatitis C epidemic peaked many years ago, hepatitis C drugmakers need to find a new source of patients.

A report published in Clinical Infectious Diseases might have the solution: people who are already infected, but don't know it yet.

Current guidelines recommend testing only people who have identified risk factors such as drug use, blood transfusions before blood-bank testing began in 1992, or unexplained liver-function abnormalities, for example -- but that misses a substantial number of infected individuals. Estimates vary, but somewhere between 50% and 75% of people infected with hepatitis C don't know it.

Most probably have the risk factors, but they're unwilling to admit to the drug use, especially if it was years ago, or have forgotten about the blood infusion. Or the doctors aren't asking the right questions to identify the risk factors -- it's a touchy subject, you know.

The solution: Test everyone. You'll get a lot of negative results -- less than 2% of the population is infected -- but you'll catch those who might not have been diagnosed before they progress to serious liver problems.

The researchers plugged everything from costs to cure rates to likelihood of progression of liver disease and a lot of additional parameters into one giant formula and concluded that it would be cost-effective to screen everyone between the age of 20 and 69. Hepatitis C leads to liver cancer and other complications, and eliminating the cost of a liver transplant -- a quarter-of-a-million-dollar procedure -- can make up for a lot of $20 tests.

Sounds good, in theory

One journal article isn't going to change public policy; that will require a recommendation from the Centers for Disease Control and Prevention, which is a slow and methodical process.

If the CDC does institute universal testing for adults, hepatitis C test makers would certainly benefit. Just keep in mind that there's substantial competition out there: Abbott Labs (NYS: ABT) , Roche, Siemens, and OraSure Technologies (NAS: OSUR) all sell hepatitis C tests. They don't disclose margins on individual tests, but considering the number of players involved, I'd have to guess they aren't great.

Drugmakers developing hepatitis C treatments will be the real beneficiaries if more people are diagnosed. With the cost of treatment in the $80,000 range, each new patient is quite valuable.

That is, if they're treated

As the authors of the paper point out, screening is cost-effective -- and makes drugmakers money -- only if the patients who test positive are actually treated. Hepatitis C is a chronic infection that takes years to do any real damage in patients. Unlike cancer, where there's an immediate need for treatment, hepatitis C patients can take their time.

That could mean patients are lost to follow-up. It could also mean patients wait until drugs go off patent and there are cheap generics available before taking the drugs.

Identifying more patients is good, but they're not going to be moneymakers without the help of doctors.

Something companies can control

The cure rate of hepatitis C drugs is one of the factors that determine whether testing is worth the effort. If there were no way to treat patients, identifying infected patients would be only marginally useful.

As it is, Vertex Pharmaceuticals' (NAS: VRTX) Incivek has increased the standard of care substantially. Roche's Pegasys and Merck's (NYS: MRK) Pegintron cure about half of the patients, while adding Incivek increases that to around 70%.

As Gilead Sciences (NAS: GILD) , Abbott, and others develop better drugs, and we get closer to 100% cure rates, the benefit of testing will increase. It would be nice to have the patients waiting when the second-round of oral medications are approved, but drugmakers might have to get the drugs approved first and then show that identifying additional patients is beneficial.

While the hepatitis C market shrinks, Fool analysts have found a growing revolutionary tech market. Find out what it is and how to profit from it in our free report, "The Next Trillion-Dollar Revolution." Get your free copy by clicking here.

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Model: Broad HCV Testing Cost-Effective

By Michael Smith, North American Correspondent, MedPage Today

Published: March 16, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Broader screening for hepatitis C would be cost-effective but would not by itself markedly reduce morbidity and mortality from the virus, researchers reported.

A detailed mathematical model of the U.S. hepatitis C epidemic showed that testing most adults once would be more cost-effective than the current practice of only testing people with risk factors such as injection drug use, according to Phillip Coffin, MD, and colleagues at the University of Washington in Seattle.

In a scenario with optimal referral, treatment, and cure rates, they reported, screening 60% of the general population averted an additional 7.1% of liver-related deaths, compared with risk-factor screening, they wrote online in Clinical Infectious Diseases.

But screening is only the first step, the researchers argued -- it would have to be followed by measures to ensure patients obtained treatment.

The study is the second in recent weeks to suggest that broader screening for the virus would be a cost-effective approach.

In February 2011, researchers led by David Rein, PhD, of the social science research organization NORC at the University of Chicago in Atlanta, reported that testing all adults born from 1945 to 1965 would be more cost-effective than the current risk-factor approach.

Coffin and colleagues said the conclusions of the two studies are "similar," despite differences in methods. Their own analysis of treating just the 1945-to-1965 birth cohort also showed cost-effectiveness, they reported.

The epidemic of hepatitis C transmission peaked decades ago, but about four million people in the U.S. are currently infected with the virus and up to 75% of those don't know they have the disease, the researchers noted.

Current incidence is low but chronic infection now results in more deaths annually than HIV. In the absence of treatment, Coffin and colleagues noted, chronic infection is predicted to lead to almost 300,000 deaths from 2020 to 2029.

"The stealth epidemic of hepatitis C has finally matured, leaving a narrow window of opportunity to find those with advancing disease, connect them with care, and prevent the tragic and costly consequences of liver cancer and end-stage liver disease," Coffin said in a statement.

To see how best to find those with disease, he and colleagues used statistical modeling techniques, comparing the current risk-factor screening with broader approaches.

They reported that one-time screening of adults ages 20 through 69 would have an incremental cost per quality-adjusted life year gained (ICER) of $7,900.

The cost-effectiveness ratio for screening by birth year was actually better -- with an ICER of $4,200, compared with risk-factor screening -- if parameters such as cost, clinician uptake, and median age of diagnoses were the same.

But the impact of screening alone on liver-related deaths was not great -- about a 1% reduction for every 15% of the population screened, Coffin and colleagues reported.

Those figures could be improved, they found, with better linkage to care and treatment outcomes.

"We need a large-scale, coordinated effort to identify people with this infection and make sure they get the care they need," Coffin said.

Indeed, better screening strategies will only be of use "if efforts are implemented to increase acceptability of screening by patients and clinicians and (to) improve linkage to care," argued Sylvie Deuffic-Burban, PhD, of Université Lille Nord de France in Lille, France, and Yazdan Yazdanpanah, MD, PhD, of Hôpital Bichat Claude Bernard in Paris.

In an accompanying editorial commentary, they note that one-time screening might be preferred, because it could be done at the same time as universal HIV testing, which is now recommended both in the U.S. and France.

But they cautioned that another aspect of the analysis remains to be done -- which approach would have the least impact on overall health budgets?

"Such an analysis, which may favor one-time screening of high-risk birth cohorts because it targets a smaller number of patients, will provide additional information for decision-making in a context in which financial resources are scarce," they wrote.

The research had support from the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources.

Coffin did not report any relevant conflicts.

Editorialist Deuffic-Burban reported financial links with Roche, Janssen Pharmaceuticals, Schering-Plough, Merck, and GlaxoSmithKline. Co-author Yazdanpanah reported financial links with Abbott, Bristol-Myers Squibb, Gilead, Merck, Roche, Tibotec, and ViiV Healthcare.

Primary source: Clinical Infectious Diseases
Source reference:
Coffin PO, et al "Cost-effectiveness and population outcomes of general population screening for hepatitis C" Clin Inf Dis 2012; DOI: 10.1093/cid/cis011.

Additional source: Clinical Infectious Diseases
Source reference:
Deuffic-Burban S, Yazdanpanah Y "It is time to change the paradigm for hepatitis C virus testing" Clin Inf Dis 2012; DOI: 10.1093/cid/cis047.

Source

NICE Publishes Final Draft Guidance on telaprevir for Chronic Hepatitis C

Healthcare guidance body NICE has today (16 March) issued final draft guidance recommending telaprevir (Incivo, Janssen Cilag), in combination with peginterferon alfa and ribavirin, as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease [1].

Hepatitis C is a blood-borne virus that predominantly infects the cells of the liver. Transmission is by contact with infected blood primarily as a result of exposure through the skin to contaminated blood (for example, through intravenous drug use). The virus can cause inflammation of, and sometimes significant damage to, the liver and affect its ability to perform its many, varied and essential functions. A hepatits C infection can be categorised into 2 stages, firstly an acute infection (the first 6 months following initial infection) and secondly a chronic infection.

Figures from 2009 suggest that around 146,000 people were chronically infected with the hepatitis C virus. Genotype 1 is the most common subtype of hepatitis C in England and Wales - affecting 40-50% of people with hepatitis - and the most resistant to treatment. Poor diagnosis and compliance rates and a high annual incidence of new infection mean that CHC presents a major public health challenge, despite the availability of treatments that provide the opportunity to address this challenge.

The primary aims of treatment are to clear the virus from the blood to prevent progression of liver disease, and to prevent the transmission of the hepatitis C virus. Current NICE guidance [2] recommends pegylated interferon and ribavirin combination therapy for people with genotype 1 chronic hepatitis C.

Telaprevir inhibits the activity of the NS3/4A serine protease. Activity of this protease is essential for viral replication and may be partially responsible for the ability of the hepatitis C virus to evade clearance by the host immune system. The drug is administered orally. The final draft guidance for telaprevir recommends the drug as an option for the treatment of genotype 1 chronic hepatitis C in adults with compensated liver disease who are previously untreated or in whom previous treatment with peginterferon alfa and ribavirin has failed, including people whose condition has relapsed, partially responded or did not respond.

Commenting on the draft recommendations, Meindert Boysen, Programme Director Technology Appraisals at NICE, said: "Chronic hepatitis C can have a significant impact on a person's quality of life, particularly when if it progresses to the fibrosis and cirrhosis stage. Fear of transmitting the disease is also a concern, particularly for women of child-bearing age for whom there is a risk of transmitting the disease to their unborn child. The Committee heard that the current treatment regimen for chronic hepatitis C is often lengthy and that the side effects of treatment themselves can have a significant impact on daily life.

"The significant improvement in sustained virological response rates seen with telaprevir plus peginterferon alfa and ribavirin compared to peginterferon alfa and ribavirin alone, and its potential for shortening the treatment time from the full 48 week course needed for a virological response therefore represents a major benefit for people with chronic hepatitis C. The Committee also acknowledged the significant public health impact that a sustained virological response can have in reducing transmission of the hepatitis C virus to uninfected people. We are pleased to be able to recommend teleprevir as a cost effective use of NHS resources, alongside boceprevir for which positive draft guidance was published last week."

The draft guidance is now with consultees, who have the opportunity to appeal against it. NICE has not yet issued final guidance to the NHS.

Ends

Notes to Editors
References and explanation of terms
[1] Chronic hepatitis C infection causes initial inflammation of the liver that progresses through to gradual scarring (fibrosis) and then hardening of liver tissue (cirrhosis). Cirrhosis commonly occurs in two stages, compensated and decompensated. In the first stage of cirrhosis, the liver can compensate for the damage and still has the ability to function normally. When extensive damage occurs and the liver can no longer function normally, decompensation occurs.

[2] NICE has published the following related guidance on hepatitis C:

•Peginterferon alfa and ribavirin for the treatment of chronic hepatitis C (part review of NICE technology appraisal guidance 75 and 106). NICE technology appraisal guidance 200 (2010).
•Peginterferon alfa and ribavirin for the treatment of mild chronic hepatitis C. NICE technology appraisal guidance 106 (2006).
•Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C. NICE technology appraisal guidance 75 (2004).
About the draft guidance
1. Approximately 15% of those infected with hepatitis C virus will naturally clear the virus from their body and experience no long-term effects from the infection. However, for the remaining 85% a chronic infection will develop. 80%(68) of those who develop a chronic infection will remain stable but the remaining 20% (17) will go on to develop liver cirrhosis, of whom 25% (4) will either progress to hepatocellular carcinoma, require a liver transplant, or die.

2. Figures from 2009 suggest that around 250,000 people were infected with the hepatitis C virus, of whom 146,000 were chronically infected. Hepatitis C is more common in men and in people aged 25-44 years. In England, prevalence studies suggest that people of South Asian family origin are at an increased risk of having hepatitis C infection.

3. In 2008, the Department of Health estimated that 68,000 patients with hepatitis C infection had been diagnosed and 4,800 had been treated.

4. The aims of treatment are:

•To eradicate the hepatitis C virus in the individual
•To prevent progression of liver disease and development of liver cancer
•To prevent transmission of hepatitis C virus
5. The Committee accepted that the most plausible ICERs for telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone were £18,000 and £10,000 per QALY gained for the previously untreated and previously treated patients.

6. Telaprevir is priced at priced at £1866.50 for a 1-week, 42-tablet pack (excluding VAT; ‘Monthly Index of Medical Specialities' [MIMS] January 2012). This equates to a maximum of £22,398 for a 12-week course of therapy. Costs may vary in different settings because of negotiated procurement discounts.

7. NICE is also appraising boceprevir (Victrelis, Merck Sharp & Dohme) for this indication.

8. The SMC has published guidance on telaprevir for this condition: www.scottishmedicines.org.uk/SMC_Advice/Advice/742_11_telaprevir_Incivo_experienced_patients/telaprevir_Incivo and www.scottishmedicines.org.uk/SMC_Advice/Advice/743_11_telaprevir_Incivo_naive_patients/telaprevir_Incivo

About NICE
The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health

NICE produces guidance in three areas of health:

•public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
•health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
•clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
NICE produces standards for patient care:

•quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
•Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients
NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.

This page was last updated: 13 March 2012

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CROI 2012: Treating HIV During Pregnancy Also Lowers Risk of Transmitting Hep C to Baby

March 16, 2012

by Tim Horn

For women living with HIV and hepatitis C virus (HCV) coinfection, using HIV antiretroviral (ARV) therapy during pregnancy may lower the risk of transmitting both viruses to their infants, according to encouraging new data presented Tuesday, March 6, at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

Most research on mother-to-child transmission (MTCT) of hepatitis C was done before there was widespread access to combination ARV therapy among pregnant women living with HIV and HCV. In earlier years of the HIV pandemic, up to 19 percent of babies born to mothers living with HIV/HCV coinfection acquired HCV, versus 2 to 5 percent of babies born to mothers with HCV alone. Although combination ARV treatment has been proved to reduce MTCT of HIV, little has been known about the effects of modern-day HIV treatment combinations on MTCT of HCV.

Continue Reading …

Hepatitis C Incidence Increasing in Younger People

From Medscape Medical News

Emma Hitt, PhD

March 16, 2012 — Pennsylvania is reporting an increased incidence of hepatitis C infections in people 15 to 34 years of age, according to results presented at the International Conference on Emerging Infectious Diseases 2012, held in Atlanta, Georgia.

Sameh Boktor, MD, adult viral hepatitis prevention coordinator at the Bureau of Epidemiology, Pennsylvania Department of Health, in Harrisburg, presented the findings.

"This has major consequences for the control of this disease, and has implications for the long-term treatment of infected individuals," Dr. Boktor and colleagues say.

"Our findings are similar to those recently reported from Massachusetts and elsewhere," they add.

"Clinicians need to consider hepatitis C in their younger patients, especially those engaging in behaviors such as IV drug use," Dr. Boktor told Medscape Medical News.

To assess the incidence of hepatitis C, the researchers reviewed Pennsylvania's hepatitis C surveillance data from 2003 (the first full year of reportable data) to 2010. They compared age-specific rates of reported cases over time.

The number of newly confirmed or probable hepatitis C cases in people 15 to 34 years of age increased from 1384 in 2003 to 2393 in 2010 (from 43 to 72 cases per 100,000 people).

In addition, the proportion of cases in males in the that age group rose from 50% in 2003 to 63% in 2010.

In contrast, rates of newly reported cases in all age groups decreased from 85 to 72 cases per 100,000 from 2003 to 2010. In those 45 to 64 years of age, cases decreased from 185 to 142 per 100,000 during the same time period.

"The change in rates between 2003 and 2010 appears largest in some rural areas of Pennsylvania rather than in the 2 large urban centers," Dr. Boktor and colleagues point out.

According to Dr. Boktor, hepatitis C is considered a problem of middle age, owing to exposures that happened well in the past, particularly among those 45 to 64 years of age (the baby boomers).

"Many in the clinical and public health communities are unaware that there appears to be a new wave of hepatitis C among adolescents and young adults emerging, especially in those engaged in high-risk behaviors such as IV drug use," he said.

"Since this infection is becoming increasingly treatable, testing for hepatitis C is a very important step to ensure proper care, avoid long-term complications, and hopefully reduce the potential for subsequent transmission of the virus," he added.

Independent commentator John Bartlett, MD, professor of medicine in the division of infectious diseases at the Johns Hopkins University School of Medicine in Baltimore, Maryland, noted that "there really is not a good explanation for these findings."

"The greatest risk by far is injection drug use; it is unclear from the report if this was shown," Dr. Bartlett told Medscape Medical News. He added that hepatitis C can be transmitted by sex and tattooing, although neither transmit the infection very efficiently and probably can not explain the increase.

According to the Centers for Disease Control and Prevention, approximately 3.2 million people are chronically infected with hepatitis C, making it the most common blood-borne infection in the United States. Overall, the incidence of acute hepatitis C has declined from just under 2.50 cases per 100,000 in 1992 to about 0.25 cases per 100,000 in 2003 in the United States, with the incidence remaining stable after that.

This study was not commercially funded. The researchers and Dr. Bartlett have disclosed no relevant financial relationships.

International Conference on Emerging Infectious Diseases (ICEID) 2012: Board 75. Presented March 14, 2012.

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CEVHAP hosts agenda-setting meet on hepatitis policy

16 - 31 March 2012

While, it has taken far too long to get viral hepatitis the attention it deserves, global experts cautiously hope that with successful partnerships and learning from the HIV/AIDS experience, the Asia-Pacific region can be an example to the rest of the world in controlling viral hepatitis, reports Viveka Roychowdhury

The spread of viral hepatitis got special attention at this year's Conference of the Asia Pacific Association for the Study of the Liver (APASL) which was held in February in Taiwan. Even though viral hepatitis, especially B and C, affect approximately 340 million people across the Asia-Pacific region, most governments do not have a public health policy in place to tackle this disease. This is in sharp contrast to the efforts of HIV/AIDS advocacy, which over the last three decades, has helped to shape public health policy.

Hoping to adopt and adapt key learnings from HIV/AIDS experience, The Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP), organised the 'CEVHAP Symposium: Better health through better public policies—What Viral Hepatitis can learn from the HIV experience', on the last day of APASL. The purpose of the Symposium was to identify advocacy models that might be effectively adapted within the Asia Pacific region to lobby governments to improve public health policies to cope with the threat of viral hepatitis.

Such efforts seem long overdue. In fact it was as late as May 2010, that the World Health Assembly ratified a resolution on viral hepatitis (WHA63 R18), which for the first time recognised the full scale of the challenge and finally put viral hepatitis on the global healthcare agenda, alongside HIV/AIDS, TB and malaria. The strategy provided a framework for national governments to respond to the challenge of viral hepatitis within their own borders but also as part of a cohesive approach to tackle the disease across regions. This was followed by the World Health Organization (WHO) issuing its Global Hepatitis Strategy which combines a wide range of its products to assist countries in the development of national responses to viral hepatitis.

The CEVHAP Symposium attracted leaders from the global and Asia Pacific viral hepatitis community as well as WHO regional experts. Giving the welcome address, PASL Jia-Horng Kao, President of A2012 and Professor and Director, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine highlighted the fact that viral hepatitis is considered endemic in some parts of the Asia-Pacific region and hoped that the takeaways from the CEVHAP Symposium would assist policy makers to tackle the situation.

Prof Ding-Shinn Chen, Immediate Past Dean of the National Taiwan University College of Medicine and Chair of CEVHAP, then kicked off the Symposium, with an overview of CEVHAP's goal to be the “bridge between the medical and scientific community as well as other stakeholders.” While he admitted that the ultimate goal to eradicate hepatitis would take many years, even generations to achieve, he stressed that the short term goal is to focus on improving public health policies to reduce the health, social and economic burden of viral hepatitis in the Asia-Pacific region. He emphasised the power of collaborative partnerships, the importance of keeping patients at the centre of advocacy and ended his presentation by speculating on what would be the catalyst for mobilising a movement behind viral hepatitis.

Lessons learnt

Giving the keynote address, titled 'Learning from the Past', David L Thomas, MD, Director of the Division of Infectious Diseases, Johns Hopkins School of Medicine stressed that the viewpoint has to shift from the individual to the population. While the first lesson, is that hepatitis treatment saves lives, but unlike ARVs, this is not yet the case at the population level. Lesson two followed that improved efficacy means improved urgency, but not necessarily effectiveness. Lesson three was about reap what you sow, in terms of the impact on public health being directly in proportion to resources devoted. So while the massive resources devoted to HIV/AIDS (through PEPFAR, etc.) saw a reduction in mortality due to HIV/AIDS, the same is not the case with viral hepatitis because the political will is absent, as are the celebrities endorsing and supporting advocacy movements.

Thomas' fourth lesson is that there is more to the disease than the virus, as borne out by the fact that a study showed that there was markedly lower survival for HIV/HCV co-infected persons in Denmark during highly active anti-retroviral therapy, from 2000-2005. The fifth and final lesson is that prevention is better than treatment. He pointed out that the annual incidence of liver cancer in children in Taiwan was markedly reduced by HBV vaccination. Elimination is of course, the best form of prevention, with small pox being the best example.

Looking ahead Thomas said, controlling chronic hepatitis in the population requires more work on improving safety and efficacy of treatments, expanding testing and treatment access, educating to expand political and societal commitment. Preventing new infections, together with curing existing infections will ultimately lead to the elimination of hepatitis.

Successful collaborations

The next two speakers, Ali Sulaiman, Lecturer in Internal Medicine, Department of Medicine University of Indonesia and Benjamin Cowie, WHO Regional Reference Laboratory for Hepatitis B, VIDRL Board of Directors, Australasian Society for HIV Medicine were a classic example of the importance of leveraging partnerships and collaborations in containing diseases like HIV/AIDS in the past and now viral hepatitis. Developing countries like Sulaiman's home country Indonesia, bear the greatest disease burden and challenges due to viral hepatitis. For instance, Sulaiman said that only five per cent of hepatitis cases have access to medicine, clearly pointing to barriers that go beyond the clinic. But hopefully this will change. Sulaiman pointed out that while his government spearheaded the celebration of viral hepatitis day in the past two years, the backbone of such programmes is medicine access programmes.

Cowie spoke about translating the Australasian Society for HIV Medicine's (ASHM's) learnings from HIV to hepatitis, pointing out that while there is increasing evidence for HBV antiviral therapy as a cancer prevention strategy, antiviral effect on disease progression is reduced when resistance develops. Therefore partnerships with clinicians like ASHM's preceptorship programme, imparting primary care management of HCV for Indonesian primary care doctors and internists, are crucial. Cowie expressed the hope that maybe the Asia-Pacific region can be an example to the rest of the world in controlling viral hepatitis.

There is no doubt of the patient's role as an important stakeholder and even catalyst to policy change, hence patient advocacy groups (PAGs) have a very crucial role. Speaking about the development of PAGs in viral hepatitis, Charles Gore, President, World Hepatitis Alliance, himself a patient of hepatitis C and cirrhosis, spoke about the need to raise viral hepatitis up the agenda and the role conferences like APASL and associations like CEVHAP need to play to build up the patient voice in the Asia-Pacific region.

The WHO viral hepatitis strategy

Professor Stephen Locarnini, Head, WHO Regional Reference Laboratory for hepatitis B, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia and Joint Secretary, CEVHAP outlined the four key priorities of the WHO Viral Hepatitis Strategy. Partnership, mobilisation and communication come first, followed by collection of data to help shape for policy and action. Prevention of transmission forms the third axis followed by screening, care and treatment.

Locarnini cautioned that there were many challenges, not least the need to fully staff the WHO HQ team as well as fully fund the 2012-2013 work plan. Operationalising the global hepatitis network, translating the HQ strategy at the regional level, contributing to country strategy and technical support as well as finally producing results and actually impacting viral hepatitis are the many challenges in the path ahead.

Speaking as the co-founder of CEVHAP, he summarised its work since its inception, saying that it has established a solid base, with strong membership and a unique position. Current and planned projects can provide strong data and evidence to influence policy but will require strong follow-up on the ground. Therefore he stressed that it is imperative that CEVHAP works closely with other groups at global, regional and national levels to share data and best practices and maximise impact

The Symposium concluded with a panel discussion, chaired by Locarnini, with the panellists (Gore, Rosmawati Mohamed, University of Malaya, Kuala Lumpur, Henry Lik-Yuen Chan, The Chinese University of Hong Kong and Jack Wallace, La Trobe University, Melbourne) giving their views on what the viral hepatitis sector needed to catalyse a movement.

viveka.r@expressindia.com

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