Ira Jacobson, MD, Vincent Astor Professor of Clinical Medicine at the Weill Medical College of Cornell University, describes how the approval of two new protease inhibitors have changed the current standard of care for hepatitis C.
Click Here To Listen; Podcast
"Hepatitis C has become a very exciting field to be in after many years, really over a decade, of being on a plateau of the available therapy," said Jacobson. "We now have two novel protease inhibitors which were both approved by the FDA in May 2011."
Vertex thoughts on the evolution of hepatitis C treatment -Earnings Call Transcript
With INCIVEK, we believe we have set a high bar in the treatment of hepatitis C. Our goal is to sustain leadership in this disease. That means continuing the very successful launch of INCIVEK, continuing our efforts to explore new ways of achieving high viral cure rates and further shortening treatment duration, and continuing to improve treatment options and outcomes for people living with hepatitis C...
Notes from the Field: Risk Factors for Hepatitis C Virus Infections Among Young Adults --- Massachusetts, 2010
October 28, 2011 / 60(42);1457-1458
During 2002--2009, rates of newly diagnosed hepatitis C virus (HCV) infection increased from 65 to 113 cases per 100,000 population among persons aged 15--24 years in Massachusetts (1). Accordingly, the Massachusetts Department of Public Health (MDPH) and CDC interviewed persons aged 18--24 years with HCV infection reported to MDPH during July 1--December 31, 2010, to elicit detailed information regarding demographic, clinical, and risk characteristics.
Of the 394 patients indentified, 193 (49%) had a valid telephone number; of those 193 patients, 101 (52%) did not answer after three call attempts, 19 (10%) were either in a drug treatment facility or incarcerated, 19 (10%) refused to participate, 31 (16%) agreed to participate but did not come on the scheduled interview day, and 23 (12%) completed the interview. An additional five persons aged 18--24 years with diagnosed HCV infection during July 1-- December 31, 2010, but not reported to MDPH, were interviewed in a correctional facility, where they were incarcerated.
Mean age of the 28 respondents was 21.9 years (range: 19--24 years); 15 (54%) patients were female, 23 (82%) were white, nine (32%) did not finish high school, nine (32%) were unemployed, and 25 (89%) had health insurance. Twenty-six (93%) had used drugs; of these, 100% reported marijuana use, with a median age of initiation of 13 years (range: 9--17 years); 92% reported opioid analgesic abuse (oxycodone and/or Oxycontin), with a median age of initiation of 17 years (range: 12--23 years); and 89% reported heroin use, with a median age of initiation of 18 years (range: 14--21 years). Nearly all respondents (95%) used opioid analgesics before switching to heroin. During the preceding 6 months, the most frequently injected drugs among respondents were heroin (50%) and opioid analgesics (30%).
Medical record reviews showed that five respondents had visited emergency departments on multiple occasions complaining of pain and were prescribed opioid analgesics. Most respondents (70%) reported sharing syringes and drug paraphernalia within networks of injection drug users that included persons with known HCV infection (43%). One in four respondents reported never being informed of their HCV infection by their health-care provider, and 11 (39%) were tested for HCV in a drug treatment program or during incarceration.
The findings in this report are subject to at least three limitations. First, only a small number of persons agreed to be interviewed, which limits the ability to generalize these findings. The low response rate might be attributed, in part, to the characteristics of the targeted population (young injection drug users) coupled with lack of provision of incentives. Second, comparison of the demographic and clinical characteristics of persons who were interviewed with those who could not be interviewed was not possible because information was lacking for nearly 60% of the 394 hepatitis C cases reported during July 1--December 31, 2010. However, of those cases with available information, 229 (58%) occurred among females and approximately 80% occurred among whites, which is consistent with the demographic characteristics of interviewed respondents. Finally, persons with HCV infection who were in drug rehabilitation centers could not be interviewed because of federal confidentiality regulations specific to these centers.
Consistent with other studies, most respondents reported opioid analgesics abuse before switching to heroin (which is less expensive) (2,3). Health-care providers should routinely ask about prescription and illicit drug use and screen all persons with risk factors for HCV infection, regardless of age (4). They also need to be aware of warning signs of prescription opioid and drug abuse, such as frequent complaints of pain and request for opioids. Drug treatment programs and prisons are potential venues for education regarding the risk for hepatitis C from sharing needles and other injection paraphernalia and for providing vaccination against hepatitis A and B. School and community-based education programs also are needed to prevent initiation of illicit and prescription drug use (5). Several harm reduction interventions have been conducted to assess the effectiveness of reducing incidence of both human immunodeficiency virus and HCV infection. Overall results from a recent meta-analysis did not indicate a statistically significant decrease in incident HCV infection from a single programmatic strategy; however, the results did indicate that combined interventions were effective (6). Thus, combining current interventions and identifying new evidence-based approaches to preventing drug use and unsafe injection practices in young adults are needed to control and prevent HCV infections.
Reported by; Daniel Church, MPH, Kerri Barton, MPH, Franny Elson, MS, Alfred DeMaria, MD, Kevin Cranston, MDiv, Massachusetts Dept of Public Health. Norma Harris, PhD, Stephen Liu, MPH, Dale Hu, MD, Deborah Holtzman, PhD, Scott Holmberg, MD, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; Rania A. Tohme, MD, EIS Officer, CDC.
Corresponding contributor: Rania A. Tohme, rtohme@cdc.gov, 404-718-8577.
References
- CDC. Hepatitis C virus infection among adolescents and young adults---Massachusetts, 2002---2009. MMWR 2011;60:537--41.
- Lankenau SE, Teti M, Silva K, Bloom JJ, Harocopos A, Treese M. Initiation into prescription opioid misuse amongst young injection drug users. Int J Drug Policy 2011; June 19 [Epub ahead of print].
- Grau LE, Dasgupta N, Harvey AP, et al. Illicit use of opioids: is OxyContin a "gateway drug"? Am J Addict 2007;16:166--73
- CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR-19).
- National Institute on Drug Abuse. Preventing drug use among children and adolescents: a research-based guide for parents, educators, and community leaders. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health; 2003. Available at http://www.drugabuse.gov/prevention/index.html Accessed October 25, 2011.
- Hagan H, Pouget ER, Des Jarlais DC. A systematic review and meta-analysis of interventions to prevent hepatitis C virus infection in people who inject drugs. J Infect Dis 2011;204:74--83.
In Part Curing Hepatitis C -John Bartlett's Game Changers in Infectious Disease: 2011
Curing Hepatitis C -With a combination of a nucleoside and a polymerase inhibitor, Gane and colleagues[6] have shown a high rate of success in suppressing hepatitis C virus (HCV) to undetectable levels in 14 days without the need for peginterferon and ribavirin. Although based on limited sample size and long-term follow-up, these findings represent enormous progress in the field of hepatitis C treatment...
A Cure For Hepatitis C-The Pharmaceutical Companies and Us
This review covers the newly approved HCV protease inhibitors boceprevir and telaprevir, along with the promise of interferon free therapies...
Hepatitis C-Telaprevir: A Novel NS3/4 Protease Inhibitor
We evaluated the literature on telaprevir, a new, oral, covalent, reversible NS3/4A HCV protease inhibitor. A MEDLINE search (January 1996–July 2011) was performed to identify relevant clinical trials, and abstracts from hepatology and human immunodeficiency virus (HIV) conferences were reviewed. In large clinical trials, the addition of telaprevir to peginterferon and ribavirin resulted in high sustained virologic response rates in both treatment-naive and treatment-experienced patients infected with HCV genotype 1. Clinical data with telaprevir in the HIV-HCV coinfected population are emerging, as well as data on potential drug-drug interactions with this agent. Preliminary data describe the resistance profile of telaprevir; however, more information is needed in this evolving area. Telaprevir's most common adverse events included rash, pruritis, and anemia. Based on available data, this new anti-HCV drug will likely be widely used and may revolutionize the treatment of HCV-infected individuals...
Revamping a Specialty: Advanced/Transplant Hepatology
Today, many millions of Americans have liver disease, but the exact figure is unknown. An estimated 4.5 million Americans are infected with hepatitis B and C viruses. Many millions more are affected by non-alcoholic fatty liver disease, although the true incidence remains undetermined; the American Liver Foundation estimates it may be as high as 25% of the adult population. Additionally, an undetermined number of Americans are living with transplanted livers. Today, 6,000 people annually undergo liver transplants, while another 16,000 are on the waiting list.
Ten years ago, the American Board of Internal Medicine (ABIM)—after much debate—approved the designation of advanced/transplant hepatology as a distinct discipline. Backed by every major gastroenterology and liver society in the country, the specialty was created to reverse a shortage of trained hepatology professionals who were faced with growing numbers of transplant patients.
Now, as the specialty enters its second decade, its proponents once again are looking at ways to revamp training. They say new training paradigms are needed to raise the number of trained liver specialists capable of managing an increasing burden of disease that ranges from obesity-related disorders to patients on transplant lists.
“Training hepatologists is a really big issue now because the burden of liver disease in America is accelerating, and I believe is outstripping the supply of trained individuals to manage it,” said Carl L. Berg, MD, chief of gastroenterology and hepatology, and medical director of liver transplantation at the University of Virginia in Charlottesville.
Most experts point to three factors driving the crunch on hepatology services: growing numbers of patients with liver disease; markedly improved and complex therapies, which have lengthened the lifespan of those with severe disease; and no corresponding rise in the number of physicians with specialized training to care for these patients.
“There are millions of Americans with chronic liver disease, which remains clinically silent until advanced liver disease sets in,” noted Arun J. Sanyal, MD, president of the American Association for the Study of Liver Diseases (AASLD), in the organization’s monthly newsletter last year (available at www.aasld.org/news/archive/022510/Pages/default.aspx). “On the other hand, there are only a thousand or so fully trained hepatologists to serve our communities.
“If progress is to be made in eradication of liver disease and promotion of liver wellness, fixing this manpower shortage must become a national priority,” Dr. Sanyal wrote.
Additionally, the Institute of Medicine called attention to the shortage in January 2010, in a report that highlighted a marked lack of awareness, knowledge and skills among the general medical workforce regarding liver disease.
Historical Hepatology
Although crude forms of hepatology have been around since 2,000 BC (when fortune tellers examined animal livers to foretell the future), modern clinical hepatology has been around for only about 60 years.
The first liver association, the AASLD, was founded in 1950, with its inaugural meeting attended by 12 individuals. Nine years later, British physician Sheila Sherlock set up a liver center at Royal Free Hospital in London, the first of its kind worldwide. For the next 40 years, hepatology fell firmly within the specialty of gastroenterology.
After 1990, liver transplant centers proliferated, and with them, transplant patients. As a result, there was a growing need for dedicated hepatologists to care for these complex patients. In 1999, AASLD members acknowledged the need, saying that advanced/transplant hepatology should be a “distinct discipline” and more physicians trained in the field were necessary.
The emphasis in the new specialty was on liver transplantation rather than broad hepatology, said Bruce R. Bacon, MD, professor of internal medicine at Saint Louis University School of Medicine in St. Louis, in a published interview (Can J Gastroenterol 2007;21:421).
“It was thought that general hepatology remained within the purview of gastroenterology,” Dr. Bacon explained.
Since then, however, the thinking has changed.
“At the present time, it has become increasingly apparent that hepatology should be considered a distinct discipline independent from, but closely allied with, gastroenterology,” Dr. Bacon said.
Contemporary Hepatology
Today, many millions of Americans have liver disease, but the exact figure is unknown. An estimated 4.5 million Americans are infected with hepatitis B and C viruses. Many millions more are affected by non-alcoholic fatty liver disease, although the true incidence remains undetermined; the American Liver Foundation estimates it may be as high as 25% of the adult population. Additionally, an undetermined number of Americans are living with transplanted livers. Today, 6,000 people annually undergo liver transplants, while another 16,000 are on the waiting list.
Compare that to the numbers of liver specialists: About 3,376 specialists in 2007 were dues-paying members of the AASLD. Of them, only half are American-based physicians and only half of those consider the AASLD to be their primary professional society affiliation.
Because the hepatology certification exam has been offered only three times since its creation in 2004, most gastroenterologists who look after liver patients are not board-certified. In fact, only about 2% of practicing gastroenterologists have transplant hepatology certification (Elta GH. Am J Gastroenterol 2011;106:395-397).
Today, 31 accredited hepatology training programs exist in the United States, most of which train only one or two fellows per year. Of these, only 30 to 40 positions are filled annually, said John R. Lake, MD, professor of surgery and medicine, and director of the liver transplant program at the University of Minnesota, in Minneapolis. The remaining spots remain vacant.
For gastroenterology fellows, the reluctance to pursue additional hepatology training can be understandable. Hepatology training adds an extra year, after six years of internal medicine and gastroenterology. Moreover, hepatology work generally pays less than an endoscopy-based gastroenterology practice. The patients require more time, more counseling and undergo fewer procedures.
In the long term, hepatology can be a more taxing specialty for many physicians, said Vinod Rustgi, MD, clinical professor of medicine and surgery at Georgetown University Medical Center in Fairfax, Va.
“It’s very different from procedure-based gastroenterology. Hepatologists end up having to talk to their patients much more than gastroenterologists. It’s a different way of spending the day—you have to interact closely with people,” he said.
Even if gastroenterologists are committed to treating liver disease patients, there’s no real need to pursue the subspecialty certification—they can practice hepatology without pursuing the additional year of training. And no difference exists between what gastroenterologists and hepatologists can do. Both groups perform a full breadth of procedures and their practices often overlap. Nothing would preclude an expertly trained gastroenterologist with hepatology instruction from focusing his or her practice on liver disease patients. The sole exception is directors of liver transplant programs, who require very specific training in hepatology. “But that only applies to 100 people around the country,” said Dr. Berg.
Janice Jou, MD, now a hepatology fellow at Duke University, in Durham, N.C., chose to do the additional year of fellowship to become board-certified. At the time she applied, the fellowship was an easy choice. She was awarded a grant from the AASLD, which made the additional year more financially viable. She loves the patients, their complexity and acuity.
“The advice given to me was [a hepatology fellowship] is what I should do,” said Dr. Jou.
Now, however, she sometimes wonders if she made the right choice. “It’s hard to weigh the delayed gratification of doing another year of fellowship,” she said.
She adds, however, that she believes people who are pursuing an academic career should do the transplant hepatology fellowship. “I do think it is evolving and is likely to change. However, in the current climate I think that if you are serious about an academic career, it is important. This is one of the main reasons that I chose to do the extra year, as I am interested in staying in academics.”
Revamping the Program
There’s no question that the United States needs more trained physicians to treat liver patients. Ironically, it’s the same situation that the gastroenterology community hoped to address a decade ago, with the creation of the advanced/transplant hepatology fellowship and board examination. Now, again, the gastroenterology and liver societies are looking at ways to close the gap between the number of patients who need liver care and the providers available.
Hepatologists by the Numbers | |
3,444 | the number of dues-paying members in the AASLD in 2010 |
2,335 | the number of AASLD members who reside in the United States |
1,689 | the number of “regular” AASLD members, defined as any physician, scientist or researcher working in the United States, Canada or Mexico who has contributed to knowledge about the liver or biliary tract |
31 | the number of U.S. programs offering an advanced/transplant hepatology fellowship |
30-40 | the approximate number of positions filled in advanced/transplant hepatology fellowship programs annually in the United States |
7 | the number of years of postgraduate training currently required to become a board-certified advanced/transplant hepatologist |
4 | the number of fellowship grants provided by the AASLD |
3 | the number of times that the Transplant Hepatology Certification exam has been offered |
AASLD, American Association for the Study of Liver Diseases Sources: AASLD News, February 2010; AASLD staff |
In 2009, a multisociety task force on gastroenterology training made a number of recommendations on the future of gastroenterology and hepatology training (Am J Gastroenterol 2009;104:2659-2663). Among the recommendations were the creation of a competency-based curriculum, condensed training for transplant hepatologists and enhanced disease-specific training. The ABIM recently gave the go-ahead on the first of those recommendations. This winter, the board approved a pilot program that will test a competency-based curriculum and competency-based assessment program for gastroenterology and hepatology. Trainees will be tested for technical and cognitive milestones through their procedural training, which could effectively short-track their training.
This type of competency-based training is expected to expand over the coming years, said Dr. Lake. The Accreditation Council for Graduate Medical Education (ACGME) already requires residents to demonstrate competency in six core areas. Additionally, similar competency-based programs are being tested around the world in fields outside of gastroenterology. Canadian orthopedic surgeons are testing and implementing a system based on 281 competencies deemed to be of importance in the training of orthopedic surgeons (Wadey VM et al. J Bone Joint Surg Br 2009;91:1618-1622).
Discussions are ongoing to find further ways of condensing the training process for transplant hepatologists. The task force suggested that transplant hepatology training could occur during the standard three-year fellowship, with a tailored exam at the completion of training. Since 1996, gastroenterologists were allowed to subspecialize in areas other than hepatology within their three-year fellowship at certain programs, by tracking elective and research time toward their subspecialty.
“Instead of doing three years of gastroenterology and one year of hepatology, you might be able to customize your three-year program in a way where you would do roughly two years of general gastroenterology and in the final year do full-time hepatology,” said Dr. Berg.
One other option may be to allow hepatologists to train directly after internal medicine and bypass the need for training in gastroenterology. Preliminary discussions were held with the AASLD and ABIM several years ago, but the concept remains theoretical.
All experts who spoke with Gastroenterology & Endoscopy News agreed that hepatologists will never become the sole providers in liver care. “There’s simply not enough of us,” said Dr. Berg.
As liver care becomes more complicated, extra training and expertise will become important for management of some of the problems, he said. But, he added, “I still believe fundamentally that we are going to need our general gastroenterology colleagues to help us because the burden of disease is so great.
“Because the epidemic of obesity in this country—which is associated with fatty liver disease—is so great, that burden is going to just skyrocket over the course of the next decade,” said Dr. Berg.
NYC man pleads guilty to kidney trafficking
TRENTON, N.J. (AP) -- A New York man pleaded guilty Thursday to what experts said was the first ever proven case of black-market organ trafficking in the United States.
Levy Izhak Rosenbaum admitted in federal court in Trenton that he had brokered three illegal kidney transplants for New Jersey-based customers in exchange for payments of $120,000 or more. He also pleaded guilty to one count of conspiracy to broker an illegal kidney sale...
Diabetes/Insulin Resistance
Full Text- Hepatitis C Virus Infection: Molecular Pathways to Insulin resistance.
Chronic Hepatitis C virus has the potential of inducing insulin resistance and type 2 Diabetes Mellitus in vitro as well as in vivo. Structural and non-structural proteins of HCV modulate cellular gene expression in such a way that insulin signaling is hampered, concomitantly leads toward diabetes mellitus. A number of mechanisms have been proposed in regard to the HCV induced insulin resistance involving the upregulation of Inflammatory cytokine TNF-alpha, hypophosphorylation of IRS-1 and IRS-2, phosphorylation of Akt, up-regulation of gluconeogenic genes, accumulation of lipids and targeting lipid storage organelles. This review provides an insight of molecular mechanisms by which HCV structural and non-structural proteins can induce insulin resistance.
Media
Can Coffee Save Your Life?
Scientists say a cup of joe can help ward off cancer, diabetes, depression, and more. Anneli Rufus on a dozen of coffee's miraculous benefits—and a few of its scary side effects.
NEW YORK DAILY NEWS Saturday, October 29 2011, 1:51 PM
Recalled
Rite Aid Voluntarily Recalls 12 oz. Tins of Rich Fields Butter Cookies
Contact:
Consumer:
1-800-RITE-AID
Media:
Susan Henderson
717-730-7766
skhenderson@riteaid.com
October 29, 2011 - Camp Hill, PA – Working in consultation with the United States Food and Drug Administration, Rite Aid has initiated a voluntary chainwide recall of approximately 85,000 tins of butter cookies distributed by Rite Aid under the Rich Fields brand name because of the possibility of contamination with Bacillus cereus. This microorganism may cause diarrhea, nausea and/or vomiting; however, the possibility of serious adverse health consequences is remote.
The recall was initiated after the company conducted quality testing on the affected product because of an uncharacteristic odor. Customers should not eat the cookies and can return them to any Rite Aid store for a full refund. Information regarding the recall is available online at www.RiteAid.com or by calling 1-800-RITE-AID Monday through Friday from 8 a.m. to 8 p.m. EST and Saturday from 9:30 to 6 p.m. EST.
Rite Aid also is contacting customers who purchased the affected products using their wellness+ loyalty card in order to inform them of the recall.
Rite Aid Corporation is one of the nation’s leading drugstore chains with approximately 4,700 stores in 31 states and the District of Columbia.
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