July 9, 2010

Action Alert

Action Alert

(posted July 9, 2010)

The House of Representatives is about to decide the funding amount for viral hepatitis prevention Do not miss this opportunity to tell your Representative to support an increase of up to $50 million for viral hepatitis prevention in FY2011.


The House Appropriations Subcommittee on Labor, HHS, Education and Related Agencies is about to decide the funding amount for viral hepatitis prevention for the Division of Viral Hepatitis (DVH) at the Centers for Disease Control and Prevention for Fiscal Year 2011.

On July 14th, the House of Representatives will begin to mark up the FY2011 Labor-HHS-Education bill which includes funding for viral hepatitis prevention. Given a highly partisan Congress, the economy and the President’s discretionary funding freeze, we are hearing that Appropriators have been told to cut funding across the HHS agencies. The President’s FY2011 Budget proposed the slightest funding increase of $1.8 million to DVH as part of a broader $26 million initiative at the National Center for HIV, Viral Hepatitis, STD, and TB Prevention directed towards gay men, men who have sex with men (MSM) and transgender Americans at risk for HIV. While we support this increased funding and appreciate the need for these prevention programs, it does not support core prevention funding such as hepatitis B and C counseling, testing, and referral, in addition to delivering hepatitis A and B vaccine, and establishing a national surveillance system of chronic hepatitis B and C. HAP and coalition partners will continue to work with Appropriators to include broader prevention priorities in report language.

The greatest opportunity we have to fund hepatitis prevention services is in newly authorized money within health reform’s Prevention and Public Health Fund. We believe it will be an enormous missed opportunity to overlook one of the most underfunded chronic, infectious diseases that continues to take a heavy toll on the individuals infected and contribute to greater health system costs. Hepatitis services have historically been and continue to be critically underfunded and despite the new evidence-based Institute of Medicine recommendations, hepatitis received none of the $650 million in prevention and wellness funding authorized under the American Recovery and Reinvestment Act nor any of the FY2010 $500 million authorized under the Prevention and Public Health Fund.

Congressional staff have told us that any increase hinges upon Members of Congress hearing now directly from state and local constituents on why increased funding is needed. Please continue to help us fight for increased viral hepatitis prevention funding by contacting your Representative about the tremendous need in your area of the country. Please take a few minutes to make these important phone calls!


It is urgent that your calls be made immediately. Please call your Representative’s Washington, DC office. Ask to speak to the staff person who handles healthcare issues. Whether you speak to this person directly or leave a message, tell them:

“My name is and I’m a constituent of Representative . I am calling to urge your office to weigh in with Chairman Obey of the Subcommittee on Labor- HHS-Education to support increased funding for CDC’s Division of Viral Hepatitis for a total of $50 million. I urge you to invest in hepatitis prevention by leveraging funds from health reform. Hepatitis B and C affects over 5 million Americans. Chronic viral hepatitis is the leading cause of liver cancer, one of the top 10 killers of Americans every year, and the leading cause of liver transplants each year. Congress has historically cut or flat funded the Division of Viral Hepatitis. Money for prevention of hepatitis B and C is critical to increase counseling, testing and referral in order to begin to get a handle on this potentially life-threatening and expensive, chronic disease.”

You can call your Representative at 202.225.3121. You will get the Capitol switchboard. Ask to be connected to your Representative’s office.

Thanks for taking the time to make these important phone calls!

The Division of Viral Hepatitis received $19.3 million in FY2010. With this level of funding, DVH can only support states and cities with an average federal funding award of $90,000. This is only enough for a staff position of the Adult Viral Hepatitis Prevention Coordinator (AVHPC) and not for the provision of core prevention services. An estimated 65-75% of infected Americans do not know their status, compared with 20-30% who do not know their HIV status. Compared to prevention funding for HIV at $728 million, STD at $154 million and TB at $144 million, viral hepatitis is the most underfunded and defunded disease, representing less than 2 percent of the budget of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and Tuberculosis Prevention.

Policymakers must be made aware of the consequences of continued inaction. The costs to the healthcare system generated by advanced liver disease associated with chronic hepatitis C infection will increase from $30 billion to $85 billion per year. Medicare will be especially hard hit because two-thirds of Americans with chronic hepatitis C infection are baby boomers and the vast majority (75 percent) is unaware; these patients will soon age into Medicare and are likely to progress to advanced liver disease unless they are identified, evaluated and treated soon. In addition to causing 15,000 deaths each year, hepatitis will continue to be the most common cause of non-AIDS-related death in co-infected Americans with HIV with as many as 25percent co-infected with hepatitis C and 10 percent with hepatitis B. Acute hepatitis B will continue to disproportionately impact African Americans, particularly in the southern states, and chronic hepatitis B among Asian Americans where it is the leading cause of death and 10 percent remain infected. Even with a safe and effective vaccine against hepatitis B, 3,000 Americans will continue to die and roughly 1,000 babies will still be infected at birth.

The following Representatives are of great importance at this juncture since they are all Appropriators. If you live in any of these jurisdictions, it is of the utmost importance that you contact your Representative as his or her constituent to weigh in on increased funds for viral hepatitis prevention:

Jo Bonner (R)
Robert Aderholt (R)

Marion Berry (D)

Ed Pastor (D)

Lucille Roybal-Allard (D)
Barbara Lee (D)
Michael Honda (D)
Sam Farr (D)
Adam Schiff (D)
Ken Calvert (R)
Jerry Lewis (R) (Ranking Member on full Appropriations committee)

John Salazar (D)

Rosa Delauro (D)

Allen Boyd (D)
Debbie Wasserman Schultz (D)
Bill Young (R)
Ander Crenshaw (R)

Sanford Bishop (D)
Jack Kingston (R)

Michael Simpson (R)

Jesse Jackson Jr. (D)
Mark Kirk (R)

Pete Visclosky (D)

Tom Latham (R)

Todd Tiahrt (R) (Ranking Member on Labor-HHS Subcommittee)

Ben Chandler (D)
Harold Rogers (R)

Rodney Alexander (R)

Dutch Ruppersberger (D)

John Olver (D)

Carolyn Kilpatrick (D)

Betty McCollum (D)

Jo Ann Emerson (R)

Dennis Rehberg (R)

North Carolina
David Price (D)

New Jersey
Steve Rothman (D)
Rodney Frelinghuysen (R)

New York
Nita Lowey (D)
José Serrano (D)
Maurice Hinchey (D)
Steve Israel (D)

Tim Ryan (D)
Marcy Kaptur (D)
Steve LaTourette (R)

Tom Cole (R)

Chaka Fattah (D)
Patrick Murphy (D)

Rhode Island
Patrick Kennedy (D)

Lincoln Davis (D)

Chet Edwards (D)
Ciro Rodriguez (D)
Kay Granger (R)
John Culberson (R)
John Carter (R)

Frank Wolf (R)

Norman Dicks (D)

West Virginia
Alan Mollohan (D)

David Obey (D) (Chair of full Appropriations committee and Labor-HHS subcommittee)

The Hepatitis Appropriations Partnership (HAP) is a national coalition based in Washington, DC and includes community-based organizations, public health and provider associations, national hepatitis and HIV organizations, and diagnostic, pharmaceutical and biotechnology companies from all over the country. HAP works with policy makers and public health officials to increase federal support for hepatitis prevention, testing, education, research and treatment. Please contact Colin Schwartz at 202.434.8005 or cschwartz@NASTAD.org if you have any questions or need additional information.


Rapid virological response as a predictor of sustained response in HCV-infected patients with persistently normal alanine aminotransferase levels: A multicenter study

Journal of Viral Hepatitis

Early View (Articles online in advance of print)
Published Online: 8 Jun 2010
© 2010 Blackwell Publishing Ltd
C. Puoti 1 , G. Barbarini 2 , A. Picardi 3 , M. Romano 4 , A. Pellicelli 5 , A. Barlattani 6 , F. Mecenate 7 , R. Guarisco 1 , O. M. Costanza 8 , L. Spilabotti 1 , L. Bellis 1 , M. E. Bonaventura 9 , O. Dell' Unto 1 , M. G. Elmo 10 , A. M. Nicolini 1 , L. Nosotti 11 and F. Soccorsi 5 , on behalf of the Club Epatologico Ospedaliero (Hospital Liver Club, CLEO)

1 Department of Internal Medicine and Liver Unit, Marino Hospital, Rome ; 2 Department of Infectious Diseases, San Matteo Hospital, Pavia ; 3 Liver Unit, Campus Biomedico University ; 4 Liver Unit, Sandro Pertini Hospital ; 5 Liver Unit, San Camillo Hospital ; 6 Liver Unit, San Giacomo Hospital ; 7 Liver Unit, Villa Betania Hospital ; 8 Molecular Biology Unit, Marino General Hospital, Rome ; 9 Department of Infectious Diseases, Rieti Hospital, Rieti ; 10 Department of Mental Health, Local Health Centre RM- A ; and 11 Department of Preventive Medicine of Migration, San Gallicano Hospital, Rome, Italy

Correspondence to Claudio Puoti, MD, Department of Internal Medicine and Liver Unit, Marino General Hospital, Via XXIV Maggio 5, 00047 Marino, Rome, Italy.
E-mail: puoti@epatologia.org

HCV • normal ALT • peginterferon • rapid virological response • ribavirin • sustained virological response

Summary. Rapid virological response (RVR) is now considered the strongest predictor of sustained virological response (SVR) in patients with HCV undergoing antiviral treatment, and thus, shorter antiviral treatment for these patients has been suggested. However, no data exist on the predictive value of RVR in HCV carriers with normal ALT values. A total of 137 patients with persistently normal ALT treated with peginterferon alfa 2a and ribavirin were studied. Fifteen patients dropped out early because of side effects, and in 10 patients with HCV-1 treatment was discontinued because of lack of early virological response (EVR). RVR was observed in 68% of the patients (42% patients with HCV-1, 90% HCV-2 and 64% HCV-3). An end-of-treatment response was observed in 86% of the patients (68% HCV-1, 100% HCV-2 and 91% HCV-3). SVR was maintained in 91 patients (46% HCV-1, 97% HCV-2 and 82% HCV-3). Overall, 92% patients with rapid response did obtain HCV eradication vs only 38% of those without rapid response. HCV-1 patients with baseline HCV RNA <400 × 103 IU/mL were more likely to achieve RVR and SVR than those with higher HCV RNA levels. We conclude that patients with genotype 1 and normal ALT who achieve HCV RNA negativity at week 4 may have a higher probability of eradicating their infection. Because of the concomitant favourable demographic and virological features often found in this particular subset of patients, the duration of therapy in these people might be shortened in the case of RVR. Persistently normal alanine aminotransferase levels patients with genotype 2 or 3 have a high chance of achieving SVR, so retesting of HCV RNA during treatment may have no additional practical value in these subjects.

Received January 2010; accepted for publication February 2010

10.1111/j.1365-2893.2010.01319.x About DOI

Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection

Journal of Viral Hepatitis

Early View (Articles online in advance of print)
Published Online: 1 Apr 2010
© 2010 Blackwell Publishing Ltd

C. Pedersen 1 , Å. Alsiö 2 , M. Lagging 2 , N. Langeland 3 , M. Färkkilä 4 , M. Rauning Buhl 5 , K. Mørch 3 , J. Westin 2 , P. Sangfelt 6 , G. Norkrans 2 and P. Brehm Christensen 1 for the NORDynamicIC Study Group

1 Department of Infectious Diseases, University of Southern Denmark, Odense C, Denmark and Department of Infectious Diseases, Herlev Hospital, Copenhagen, Denmark ; 2 Department of Infectious Diseases, Göteborg University, Göteborg, Sweden ; 3 Department of Infectious Diseases, Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway ; 4 Department of Gastroenterology, Helsinki University, Helsinki, Finland ; 5 Department of Infectious Diseases, Skejby Hospital, Aarhus University, Aarhus, Denmark ; and 6 Department of Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden

Correspondence to Court Pedersen, Department of Infectious Diseases Q, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. E-mail: court.pedersen@ouh.regionsyddanmark.dk

drug concentration • hepatitis C • ribavirin • treatment

Summary. In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
Received October 2009; accepted for publication January 2010

10.1111/j.1365-2893.2010.01303.x About DOI

With Appreciation

I thought this was a truly special story and wanted to share it.
If only we had alot more Drs. like this.

A Piece of My Mind

Vol. 303 No. 18, May 12, 2010

With Appreciation

Ram Y. Gordon, MD
Flourtown, Pennsylvania

JAMA. 2010;303(18):1790-1791.

I was in practice only three months when I met him. I had just finished my cardiology fellowship and, insecure about my lack of experience, strove for a serious, professional demeanor. My tie was straight, shirt pressed, white coat starched and buttoned. Above all, I sought to establish and maintain the boundaries of the patient-physician relationship.

"Mr M is an 82-year-old male with hypertension, hyperlipidemia, and chronic Lyme disease who presents with dizziness." His blood pressure was high and his ECG showed an asymptomatic atrial tachycardia. His stress test revealed ischemia and I referred him for cardiac catheterization.

He wrote me a note:

I am clear that you recommended I go ahead with the procedure. I "heard" that and paid attention. Yet I am making the decision not to go ahead based on what I feel I can do right now. I value and trust and feel comfortable with you, professionally and personally, and hope you will not write me off because I could not do what you recommended I do. I need to count on you for ongoing advice, expertise, help, and perspective. I will endeavor to be a good patient even though this decision will seem to you a mistake on my part. Yet I feel right about this decision.

I was surprised by his choice and was touched that he had written me with such eloquence. It was the first of many letters I would receive from him.

Mr M eventually acquiesced and underwent catheterization, which revealed coronary disease. We elected to treat it medically. Shortly thereafter, a letter arrived:

As has happened each time, I left you yesterday with added confidence, trust, zing, and a feeling that things-are-going-to-be-all-right. I know the cautions, but I also know the feeling and I am grateful to you for it.

Several months later, another note read:

I look forward to my appointments with you. Our conversations are good for my morale and good cheer, as well as my physical health.

Fifteen months after his initial visit, his blood pressure and lipids were controlled. His supraventricular tachycardia, which we called his "friend," as in "your friend was here, but now he's gone," had not affected his left ventricular function. He had chronic kidney disease and his legs were occasionally wobbly, but he otherwise felt well. A brief note from him read:

As you’ve known for quite a while now, I look to you with confidence and trust, an ace pro who cares and heartens, someone who is good news in this world.

Several months later, after an inpatient stay for a respiratory tract infection, he wrote:

I like reminding you of how much I value and honor your genuine commitment, the feeling you give of really seeing and hearing and caring. It's the other end of perfunctory. I am grateful you chose the career you did, and I, among surely so many, are grateful to be "in your light."

Mr M always wore a suit, even if our appointment was the only one on his agenda. His words were measured and he spoke in a deep baritone, as if he were giving a lecture. He had a long and distinguished career as an educator, teaching English at a local high school before becoming a nationally renowned advocate of teaching reform. He had published almost 20 books and had been featured in Time magazine. He reminded me of John Keating, the inspirational English teacher in the film Dead Poets Society. I looked forward to his appointments.

One day, he asked to learn more about me. I felt uncomfortable. He was my patient, not my friend. Our relationship, while cordial and warm, was one of physician and patient, and I was fairly certain that this line should not be crossed. But this request, from this particular patient, felt somehow different. On his next visit we discussed his stable cardiac disease and then spent 40 minutes talking about me. He was an expert interviewer and sought details of my life, my interests, and my choice of medicine as a career. I let him in.

I told him about my blue-collar Pittsburgh roots and the influence of my father, an ophthalmologist, who was the first person in his family to go to college. I told him that, like all children of physicians, I felt a constant unconscious pressure to go into medicine and was unsure of that decision until I saw patients with my father when I was 21 years old. On that day, I fell in love with the patient-physician interaction, and the marriage of science, art, and interpersonal relationships that defines clinical medicine. I told him about my mother's nurturing and about my gold-hearted grandfather, who should have been a social worker, but instead pumped gas for a living. I told him about meeting my wife in college and about my three children. When the conversation was over, and other patients were waiting, we parted. I felt that I had shared something special, something of myself, with a "friend."

I received a handwritten note several days later:

I have played through that wonderful conversation we had again and again in my mind—it's the scene from a joyous movie—us there in your office, you visiting with your father's patients for the first time, the extraordinary relationship with your grandfather and mother, your clarity from each, in what your work was going to be, and your joy in it. Often, people are moved most by stories of sadness or frustration or struggle. What was so moving to me about that conversation was that it was a story of extraordinary happiness. You were and are blessed, and so are the many of us who visit your orbit.

As a physician, I have always felt an obligation "to try and reach" every patient. Now, with Mr M, our relationship had grown closer.

Thereafter, his appointments became joyous reunions. Neuropathy had affected his fine motor movements, and I helped him button his dress shirt and adjust his tie. We would part with a hug, and his visit would lift my spirits for the rest of the day.

Although he was modest, I eventually persuaded him to share more about himself. He had a son and daughter, and two beloved granddaughters. He lived locally but had been born in his parents' bedroom in New Hampshire. He was valedictorian of his class and a champion tennis player in high school and had majored in French at a top liberal-arts college.

And, early in our discussions, it became obvious that he loved classic films. One visit, we discussed Frank Capra's It's a Wonderful Life, one of my favorite movies. He nonchalantly mentioned that he and Capra were good friends, and we talked for several minutes about their relationship. A few days later The It's a Wonderful Life Book by Jeanine Basinger was waiting for me on my desk. In it, the inscription read:

To my distinguished cardiologist, princely fellow, valued encourager, and friend. Like George Bailey, you are "the richest man in town."

I once mentioned that I shared a birthday with Fred Astaire and that my 5-year-old daughter loved his classic film Top Hat. Several days later, the complete Fred Astaire DVD series arrived on my desk with a warm note. Other movies followed and with each, a note highlighting some of the classic scenes, dances, and songs. Although I was deeply moved, I begged him on several occasions to stop giving me gifts. He insisted that it gave him great joy to think of me watching some of his favorite movies with my family. I felt he was sharing part of himself with me and accepted the films, knowing he would not take no for an answer.

Recently, I saw him for the final time in my office. A note followed:

I wonder how many people walk out of an appointment with their doctor feeling healthier, happier, more affirmed, more zesty, than when they went in. I look forward as much to the conversations—they are pure gold as far as I’m concerned. I am grateful I know you. With appreciation, Mr M.

Two months later, he developed a fever and chills but delayed going to the emergency department so that he and his wife could finish watching The Ghost and Mrs Muir on a Sunday afternoon. He was admitted and quickly transferred to the ICU. His last words to me before being intubated were "There's my fine, princely fellow." He spent the final two weeks of his life sedated and on hemodialysis. Finally, his family could bear it no longer and withdrew care, giving him the peaceful and dignified death he deserved.

His death hit me like a ton of bricks. I felt as though I had lost a grandfather. I was his physician, and his cardiac issues always came first. But his office visits, telephone calls, and letters were special gifts. I could not deny their importance to me. My medical training had imprinted on me the principle that evenhanded distance is the appropriate relationship between physician and patient. I wondered if we had crossed any lines that reduced my medical objectivity. Had I served him well as his cardiologist? Had I become too close to a patient?

Ultimately, I found peace in the realization that medicine is an art and that interpersonal relationships are at its core. Mr M was an exceptional person. To deny his proffered "friendship" would have been to miss out on an amazing relationship with a fellow human being. Understanding his nature also made me a more effective physician. On some level, I used these insights to build trust, gain his approval, and improve his adherence to a complicated medical regimen. His survival as a patient was built partially on his belief in me. I never met him socially nor did I share any activities with him outside the professional office setting. Nevertheless, I was deeply moved when his family invited me to sit with them during Mr M's memorial service. Shortly after his death, I received a beautiful bouquet of flowers and a note, written in an unfamiliar hand:

Dear Dr Gordon,
How do you tell someone they make a life difference to you?
You are, and have been, such a "special" light in our lives.
Please know that Mr M and I love you dearly.
Sincerely, Mrs M

With Mr M's passing and my reaction to it, I felt compelled to address a question: What did this relationship mean to me? The answer did not come easily and required some earnest soul-searching. In the end, I realized that his many medical problems challenged me to grow as a young physician; his remarkable character and life story inspired me to grow as a person.

Acknowledgment: I thank Jerold, Elizabeth, and Assaf Gordon and Rachel Ledewitz Gordon for their thoughtful comments and review of this essay. I am also deeply indebted to Mrs M and her family for their kindness in allowing me to share Mr M's story.

A Piece of My Mind Section Editor: Roxanne K. Young, Associate Senior Editor


Improper Anesthesia Practice Causes Hepatitis Outbreak

Anesthesiologist reused contaminated single-use propofol vial on multiple patients

Publish date: Jul 9, 2010

FRIDAY, July 9 (HealthDay News) -- An anesthesiologist who reused a contaminated single-use propofol vial on multiple endoscopy patients caused an outbreak of hepatitis infection affecting 13 patients at two clinics, according to a report published in the July issue of Gastroenterology.

Bruce Gutelius, M.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues investigated outbreaks of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients at the two clinics who had received anesthesia from the same anesthesiologist. The investigators reviewed medical charts, conducted patient interviews and site visits, and performed infection control assessments. The investigators also did molecular sequencing of available patient isolates.

At one clinic, the researchers identified six cases of HCV infection and six cases of HBV infection, and at the other clinic, one case of HCV infection; all the cases were associated with the outbreak. HCV quasispecies sequences from the patients were found to be nearly identical (96.9 to 100 percent) to those from the patients considered to be the infection source. The investigators write that the anesthesiologist used a single-use vial of propofol on multiple patients, and conclude that the likely cause of the viral transmission was the reuse of syringes to redose patients, which contaminated the vials for later patients.

"Gastroenterologists are urged to review carefully the injection, medication handling, and other infection control practices of all staff under their supervision, including providers of anesthesia services," the authors write.

Full Text (subscription or payment may be required)


Also See:
Hepatitis C Virus Infections from Unsafe Injection Practices at an Endoscopy Clinic in Las Vegas, Nevada, 2007–2008

A Guide to Clinical Trials

A researcher looks at a blood smear under the microscope.

What Is a Clinical Trial?

A clinical trial is a research study involving human volunteers to evaluate new ways to prevent, diagnose, or treat diseases. Clinical trials help determine if experimental treatments are safe, effective, or better in some way than standard treatments.

What Are the Benefits of Participating in a Clinical Trial?

Clinical trials are essential to the advancement of medicine. By participating in a trial, a patient may have access to a treatment that is new or better than the standard treatment. By participating in a trial you are also helping others who may benefit from the findings in the future. Some patients also receive free medical care or are paid for their participation.

Why Is It Especially Important for Female and Minority Patients to Participate?

Diseases affect everyone, but not in the same way. Therefore, it is important to have people of all races, ages, backgrounds, and genders participate so that the best way of preventing, diagnosing, or treating every kind of disease for every kind of person can be discovered.

Are Clinical Trials Safe?

Before an experimental treatment can be applied to people, it is carefully studied in the laboratory to determine its effectiveness and safety. Clinical trials are reviewed at both the national level by the Food and Drug Administration (FDA) and at the local level by an institutional review board (IRB). Each hospital or clinic where a clinical trial is to take place has an IRB made up of health-care professionals, patient advocates, and community leaders who review the trial for safety and fairness.

Possible participants are also carefully screened – by thorough analysis of a patient’s medical history, physical examinations, and possibly other tests – to ensure that they are the best possible candidates for the experimental treatment. During the trial, patients are carefully monitored to track how the treatment is affecting their condition. Since participation in a clinical trial is voluntary, a patient can stop at any time for any reason.

What Should I Consider Before Participating in a Clinical Trial?

Before participating, you must be provided with an “informed consent” document explaining the risks and potential benefits of the trial. Be sure to read over this information carefully. It is important to fully understand the purpose of the trial and what to expect.

You will want to find out if the treatment will interact with any of your current medications or affect any other medical conditions you may have. You should be informed about what tests or procedures, such as biopsies or blood draws, will be performed, and you should consider your comfort level with what will be done. Also, think about whether you are prepared for any anticipated side effects, pain, or discomfort that may be involved.

Another consideration is how the trial will affect your daily life. Think about how long the study lasts, if it will fit in your work schedule and personal life, and if you can commit to it. Will the hours at the clinic require that you take time off work? How many visits will be involved?

If you do decide to participate, you will be required to sign an informed consent document, and a copy will be given to you. The document will include the contact information for someone you can call should any questions or concerns arise during the trial.

Are There Costs Associated With Participating in a Clinical Trial?

This is an important question you should discuss with your doctor. There may be extra costs for participating in a study that may or may not be covered by your insurance carrier. Some examples of extra costs include additional doctor visits, special blood tests, or the cost of administering experimental treatments.

Are There Different Types of Clinical Trials?

Yes, clinical trials are classified into phases as described below:
  • Phase 1: These trials constitute the initial testing in humans and usually involve a small number of patients. The primary goal of Phase 1 trials is to demonstrate the safety of the drug or drugs being given. Sometimes Phase 1 trials test the safety of a new drug under development as well as dosage and frequency of administration; others test the safety and efficacy of a particular dosage when two or more drugs are given in combination.
  • Phase 2: Once a drug or a combination of drugs is shown to be safe in initial Phase 1 trials, it has to be shown to be effective – the primary goal of Phase 2 trials. These trials are generally longer, typically lasting several months and involve more people, up to several hundred, to prove that the drug or combination of drugs is effective in a larger patient group.
  • Phase 3: This type of trial involves large-scale testing in several hundred to several thousand people for a thorough understanding of a treatment’s benefits and side effects in a wide range of patients. Phase 3 studies are usually “randomized” studies in which a patient is randomly assigned to either the standard arm (treatment that has been approved as the current standard therapy by the FDA) or to the experimental arm (patients are given a new drug or new combination of drugs). The assignment is made by a computer or other coinflip mechanism. If the standard treatment with a new drug is being compared to the standard treatment alone, patients in the standard arm may be given a placebo (an inactive substance that has no medicinal value) in conjunction with the standard therapy while patients in the experimental arm will receive the standard therapy in conjunction with the new therapy. The FDA usually requires a successful Phase 3 study showing that a new treatment is better than the standard of care before they will consider the treatment for FDA approval.
  • Phase 4: Further analysis of a treatment is considered in these types of trials, exploring such issues as cost-effectiveness, long-term effectiveness, or how a drug affects a patient’s quality of life.
These four phases describe treatment trials. There are many other types of trials in which patients may be asked to participate, such as prevention, diagnostic, screening, and quality-of-life trials.

How Can I Find a Clinical Trial?

There are many Web sites that list current clinical trials for a variety of diseases and conditions. ASH recommends the following:

Talk with your doctor to find out if joining a clinical trial is right for you.


Consensus Interferon (Infergen) Label Changed to Include Data on Dosing with Ribavirin

SUMMARY: The U.S. Food and Drug Administration (FDA) this week announced that the label information for consensus interferon alfa, also known as interferon alfacon-1 or Infergen, for the treatment of chronic hepatitis C has been updated to include new information about using the drug in combination with ribavirin and weight-based dosing, as well as which patients are unlikely to benefit from treatment. Use of Infergen as monotherapy is not recommended unless a patient is unable to take ribavirin.
Below is the text of an FDA announcement describing the changes.

Infergen (interferon alfacon-1) Label Revision

On July 2, 2010, FDA approved revised labeling for Infergen (interferon alfacon-1) to include information on combination therapy with weight-based dosing of ribavirin. The label was placed in PLR (Physicians Labeling Rule) format and the major labeling changes include revisions to the following sections:

1) Indications and Usage section to include information describing when patients are unlikely to benefit from retreatment. This section reads as follows:

INFERGEN (interferon alfacon-1) is indicated for treatment of chronic hepatitis C in patients 18 years of age or older with compensated liver disease. This indication is based on clinical trials conducted using INFERGEN as monotherapy prior to the time that combination treatment was the standard of care and on a single trial evaluating INFERGEN in combination with ribavirin in patients who failed to respond to previous treatment with a pegylated interferon and ribavirin.

The following points should be considered when initiating treatment with INFERGEN:
  • Use of monotherapy with an interferon such as INFERGEN for the treatment of hepatitis C is not recommended unless a patient is unable to take ribavirin.
  • The safety and efficacy of the combination of INFERGEN/ribavirin in treatment-naive patients or in patients co-infected with HBV or HIV-1 have not been evaluated.
  • Patients with the following characteristics are less likely to benefit from retreatment with combination therapy: response of < 1 log10 drop HCV RNA on previous treatment, Genotype 1, high viral load (> 850,000 IU/mL), African American race, and/or presence of cirrhosis.
  • No safety and efficacy data are available for treatment of longer than one year.
2) Dosage and Administration section was updated to include dose recommendations for retreatment in combination with weight-based dosing of ribavirin for the treatment of chronic hepatitis C as follows:
Combination Treatment with INFERGEN/Ribavirin Dosing
The recommended dose of INFERGEN is 15 mcg daily administered as a single subcutaneous injection in combination with weight-based ribavirin at 1,000 mg-1,200 mg (< 75 kg and >75 kg) orally in two divided doses for up to 48 weeks. [see Clinical Studies (14.3), Medication Guide for instructions].
Ribavirin should be taken with food. INFERGEN/ribavirin should not be used in patients with creatinine clearance < 50 mL/min [see CONTRAINDICATIONS (4)].
Dose Modifications
If a serious adverse reaction develops during the course of treatment [see WARNINGS and PRECAUTIONS (5)] discontinue or modify the dosage of INFERGEN and/or ribavirin until the adverse event abates or decreases in severity. If persistent or recurrent serious adverse events develop despite adequate dosage adjustment, discontinue treatment. Upon resolution or improvement of the adverse reaction, resuming INFERGEN and/or ribavirin may be considered.
INFERGEN/Ribavirin Combination Therapy Dose Modifications
Stepwise dose reduction from 15 mcg to 9 mcg and from 9 mcg to 6 mcg may be necessary for serious adverse reactions.
Please refer to updated label for complete guidelines for dose modifications and discontinuation of INFERGEN and/or ribavirin based on depression or laboratory parameters.
3) The WARNINGS and PRECAUTIONS section was updated and placed in the order of importance of each toxicity of concern. Many of the toxicities are considered class labeling among the interferon products.
4) The Adverse Event section was updated to remove antiquated information and to include information about safety from the INFERGEN/RBV study (DIRECT Trial/IRHC-001 and IRHC-002).
5) Clinical Studies section was updated to include information regarding study IRHC-001/IRHC-002/DIRECT Trial. Specifically,
Subsequent Treatment with Combination INFERGEN/Ribavirin
This study (DIRECT Trial/ IRHC-001 and IRHC-002) was a randomized, open-label, multi-center, US-based study comparing the safety and efficacy of two doses of INFERGEN (9 mcg or 15 mcg) administered daily plus ribavirin (1000 mg or 1200 mg weight based dosed) administered daily for 48 weeks to subjects who were nonresponders to previous pegylated interferon plus ribavirin (Peg-IFN/ribavirin) therapy. Prior non-response was defined as a < 2 log10 decline in viral load (VL) while undergoing at least 12 weeks of previous Peg-IFN/ribavirin therapy with > 80% adherence or a detectable VL at end-of-treatment after completing at least 24 weeks of therapy. Study subjects had a mean age of 50 yrs, 70% were male, mean weight of 89 kg, 19% were African Americans, 65% were Caucasians, 66% had high VL (> 850,000 IU/mL), 95% were infected with genotype 1, 54% had evidence of bridging fibrosis, 25% had evidence of cirrhosis on biopsy, and 50% had steatosis. Approximately 80% of the patients were null responders (< 2 log10 drop in viral load during their previous Peg-IFN/ribavirin therapy). The median washout period between previous treatment and day 1 of INFERGEN therapy was 448 days (15 months) and 506 days (16.8 months) for the 9 mcg and 15 mcg groups, respectively. The use of hematopoietic growth factors was not permitted in the DIRECT Trial.
In study IRHC-001, 515 subjects were randomized to INFERGEN 9 mcg plus ribavirin (n=171), INFERGEN 15 mcg plus ribavirin (n=172), or no treatment (n=172). In study IRHC-002, 144 patients in the no treatment arm of study IRHC-001 were re-randomized to either INFERGEN 9 mcg plus ribavirin (n=74) or INFERGEN 15 mcg plus ribavirin (n=70).
Subjects were treated for up to 48 weeks. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after the end of treatment using a sensitive qualitative assay (TMA LOD <10 IU/mL). None of the subjects in the no-treatment arm of study IRHC-001 achieved an SVR.
Combined SVR results from IRHC-001 and IRHC-002 according to baseline characteristics are shown in Table 8 of the package insert. The overall SVR rate for INFERGEN 9 mcg/ribavirin was 5% (13/245) compared to 95 (21/242) for INFERGEN 15 mcg/ribavirin. Based on these results, INFERGEN 15 mcg is the recommended starting dose.
6) The Contraindications, and the Animal Toxicology and/or Pharmacology section was also updated.
Additionally the Medication Guide was revised to provide information on combination therapy with weight-based dosing of ribavirin and to provide information on the risk associated with interferon therapy.
The complete revised label can be accessed at the FDA web site.
Infergen is a product of Three Rivers Pharmaceuticals, Warrendale, PA.
R Klein and K Struble, U.S.Food and Drug Administration. Infergen (interferon alfacon-1) label revision: combination therapy, weight-based dosing, and label format. Hepatitis Update. July 7, 2010.


Also See:
Three Rivers Pharmaceuticals Announces FDA Approval Of Expanded Labeling of INFERGEN®

GlobalData's report available-"Hepatitis C (HCV)–Pipeline Assessment and Market Forecasts to 2016"

The Hepatitis C (HCV) Market is Forecast to Show High Growth Until 2016


PRLog (Press Release) – Jul 09, 2010 – GlobalData’s analysis suggests that the global hepatitis C market was worth $4.4 billion in 2009. It is forecast to grow at a Compound Annual Growth Rate (CAGR) of 9.8% for the next seven years to reach $8.5 billion by 2016. The high projected growth rate is primarily attributable to a strong pipeline. The increase in the prevalence of the disease and the availability of new first-in-class therapies with better safety and efficacy profiles are expected to drive the growth of the hepatitis C market.

GlobalData analyzed the current competitive landscape for HCV drugs and found that the current market competition is weak. There are six commonly used approved products for the treatment of HCV. The combination therapy of Peginterferon alfa 2 b from Merck and Peginterferon alfa 2a from Roche are the two approved combination therapies present in the market for the treatment of HCV. Generics do not hold a major share in the market. GlobalData’s analysis of the entire competitive landscape of the branded products shows weak competition between the available treatments for HCV. The competition is weak because most products have low-moderate efficacy with low safety profiles and are branded premium or combination products. The market has a huge potential for molecules with better safety and efficacy profiles.

For further details, please click or add the below link to your browser:

GlobalData analyzed the hepatitis C pipeline and found it to be strong. The pipeline for hepatitis C consists of around 63 molecules currently in development. Most of these molecules are first-in-class and are promising better safety and efficacy profiles. There are approximately three molecules in the Phase III clinical trial development stage. For example, SCH 503034 (Merck, albinterferon alfa-2b (Human Genome Sciences, Inc. (HGS)), RG7128 (Roche) and VX-950 (Vertex and Tibotec pharmaceuticals) are among the most promising molecules in pipeline for the treatment of hepatitis C. A strong clinical pipeline coupled with high unmet needs in the hepatitis C market is expected to help sustain the market’s high growth rate during the forecast period.

The global HCV market is attractive, with high levels of unmet need. The unmet need in the market is around 70%, which is approximately $3 billion. Some of the unmet needs in this market are due to the lack of availability of effective treatment options and the moderate safety profiles of the marketed drugs. The efficacy of the marketed products in HCV market is only moderate. The safety profiles of the products available to treat HCV are low and some serious side effects are associated with the drugs that may even lead to death in rare cases.

The adverse effects of the drugs include problems with pregnancy, mental health problems, blood related disorders and autoimmune disorders. Patients using the standard interferon combination therapy to treat HCV soon develop resistance against these drugs and must wait for novel therapies to enter the market. Apart from various drugs that are available for the treatment of HCV, certain biosimilars like interferon alfa-2a and interferon beta-1a can also drive the HCV market in future. There is huge untapped potential in the current HCV market which could be captured by novel molecules, targeted to fulfill the current void left by the existing treatment options. Thus the HCV market has high potential for further research and development (R&D) activities.

GlobalData, the industry analysis specialist, has released a new report, “Hepatitis C - Drug Pipeline Analysis and Market Forecasts to 2016”. The report is an essential source of information and analysis on the global hepatitis C (HCV) market. The report identifies the key trends shaping and driving the global HCV market. The report also provides insights into the prevalent competitive landscape and the emerging players expected to cause significant shifts in the positioning of the existing market leaders. Most importantly, the report provides valuable insight into the pipeline products within the global hepatitis C sector.

For further details, please click or add the below link to your browser:

Visit our report store: http://www.globaldata.com/reportstore

GlobalData is an industry analysis specialist, providing business information products and services. GlobalData’s highly qualified team of analysts, researchers, and solution consultants use proprietary data sources, tools and techniques to gather, analyze and represent the latest and the most reliable information essential for a business to sustain a competitive edge.
GlobalData is a UK-based company with presence across North America, Europe and Asia Pacific and has a broad product offering that ranges from interactive databases, reports and custom solutions. It is a comprehensive source of insights and analysis with coverage including oil & gas, power, alternative energy, nuclear power, petrochemicals, medical equipment and healthcare industries.


Liver Enzymes: A Look at AST and ALT

From Charles Daniel, former About.com Guide
Updated September 05, 2008

About.com Health's Disease and Condition content is reviewed by the Medical Review Board

Liver enzymes allow doctors to learn about the health of your liver. There are thousands of these enzymes in the liver and blood stream, but two of them -- known as aminotransferases AST and ALT -- are especially useful for determining liver disease.
What Are Aminotransferases?

Aminotransferases are chemicals the liver uses to help make the energy-storage molecule glycogen. Aspartate aminotransferase, or AST, is found in the liver, but also the brain, pancreas, heart, skeletal muscle, kidneys and lungs. Alanine aminotransferase, or ALT, is primarily found in the liver. To remember the difference between the two, I use the "L" in ALT to remind me of the liver.

Why Are AST and ALT Useful?

Because these enzymes are found in liver cells (hepatocytes) which have lots of contact with your blood supply, AST and ALT can "leak" into the blood if the hepatocytes are damaged. Blood tests can determine the level of these enzymes in your blood and doctors can use this information to form a diagnosis. Abnormally high levels of both liver enzymes show that liver cells have been damaged, but they can't tell what caused the damage. Because AST is located in many places in the body, high levels of AST alone don't suggest liver disease (a notable, but rare, exception is Wilson's disease). However, the ratio of AST to ALT, or the level of AST compared to the level of ALT, provides many clues to what's going on inside. Based on these ratios, doctors can focus their attention on a particular kind of liver disease. Here are some common guidelines used for liver disease:
  • An AST:ALT ratio equal to one (the level of ALT is higher or equal to AST), but the levels are very high, suggests acute viral hepatitis or drug-related hepatitis.
  • An AST:ALT ratio higher than 2:1 (two times the level of AST to ALT) is very suggestive of alcoholic liver disease.
  • An AST:ALT ratio higher than one (where the level of AST is higher than the ALT) could also indicate cirrhosis in a person that doesn't have alcoholic hepatitis.
Because increased enzyme levels can be seen in other diseases (heart attack, obesity, diabetes mellitus, mononucleosis), they are just one piece of a larger puzzle. To give doctors a complete clinical picture, enzyme levels must be used with other blood tests, patient examination and medical history.
What Are the Normal AST and ALT Levels?

The normal levels of AST and ALT vary from person to person and depend on your BMI, or the ratio of your height and weight. A small amount of AST and ALT is normally in your blood, so it's really a large increase over your normal level that indicates a problem. For people with acute viral hepatitis, they might have aminotransferase levels higher than 1,000 IU/L. This stands for International Units per Liter (of blood) and is a unit of measurement that labs use for many medical tests. Common ranges for AST and ALT are:
  • AST 2-45 IU/L
  • ALT 2-40 IU/L
How Are Liver Enzymes Tested?

To test for AST and ALT, a doctor needs to order an enzyme test, which usually consists of several additional tests like albumin, bilirubin and prothrombin time. A technician will draw a sample of your blood and send it to a lab to be tested. The results are sent to your doctor.

Pratt DS, Kaplan MM. Evaluation of Liver Function. In: AS Fauci, E Braunwald, DL Kasper, SL Hauser, DL Longo, JL Jameson, J Loscaizo (eds), Harrison’s Principles of Internal Medicine, 17e. New York, McGraw-Hill, 2008.


Working With Your Liver's Clock Benefits Hepatitis C

July 6, 2010

While most of us check the time throughout the day to stay on schedule, few realize that the liver also has a timed agenda. By heeding your liver's innate clock, those with Hepatitis C can help relieve some of the extra burden on this multi-tasking organ.

by Nicole Cutler, L.Ac.

Chronic Hepatitis C is a worldwide problem, infecting the livers of an estimated four million people in the U.S. alone. Until a guaranteed cure is devised for Hepatitis C, those with the virus must make every effort to support their liver's health by relieving it of unnecessary tasks. While there are a variety of strategies employed to support liver health, one that is often overlooked is working with the liver's schedule.

In charge of a long list of life-sustaining functions, the liver is an extremely busy organ. A few of its crucial duties, include:

· Producing bile, which helps carry away waste and breaks down fats in the small intestine during digestion.

· Producing certain proteins for blood plasma.

· Making cholesterol and special proteins to help carry fats through the body.

· Converting excess glucose into glycogen for storage.

· Converting poisonous ammonia to urea (urea is an end product of protein metabolism and is excreted in the urine).

· Clearing the blood of drugs and other poisonous substances.

· Resisting infections by producing immune factors and removing bacteria from the bloodstream.

Not surprisingly, the liver can't accomplish all of its amazing feats simultaneously. All of the body's organs, including the liver, have periodic cycles where different functions are emphasized at different times. The liver is no different, with a cycle completing every 24 hours.

The Liver Cycle

Although scientists are just beginning to recognize the phases of the liver's cycle, the following appear to describe the hepatic clock:

· The liver synthesizes complex chemicals and processes toxins the most when the production of bile is lowest.

· Along the same lines, chemical synthesis and toxin processing is lowest while the liver's production of bile is highest.

· Because bile is needed for food processing, the liver makes a greater proportion during the day - and less at night.

· Bile production is assumed to be at its highest at 9am and lowest at 9pm.

· After 9pm, the liver switches to its other primary functions, synthesizing chemicals and processing accumulated toxins.

· The cycle begins shifting around 3am, when the liver slows chemical synthesis and readies itself for bile production.

· The liver cycle shifts again around 3pm, when chemical synthesis begins to increase and bile production decreases.

Thus, the liver is most prepared to aid digestion with its synthesis of bile between 9am and 9pm. This is important information for those with chronic Hepatitis C who want to work with - and not against their liver.

Practical Application of the Liver Clock

Although our busy lifestyles often dictate when we eat and when we sleep, those with Hepatitis C could benefit from scheduling necessities around their liver's needs. Since bile production is down late at night, eating a big meal past 9pm puts an additional strain on the liver. Thus, experts advise eating the last meal of the day long before the nine o'clock hour.

In addition, the liver's schedule of producing chemicals and detoxification (crucial for liver health) is best accomplished without additional demands. For this reason, most experts suggest retiring for the night close to 9pm whenever possible. Although this seems extremely early for many adults, those who try it report achieving a deeper and more restful sleep.

The liver's clock may not mesh with a modern, busy schedule. However, eating early and going to bed early cooperates with your liver's natural rhythm. By taking small steps to conform to your liver's cycle, those with Hepatitis C can remove the extra challenge that multi-tasking can place on their liver.