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Week Ending: January 9, 2010
Alan Franciscus
Editor-in-Chief
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This Issue:
January 3, 2010
Chlorophylls Effective against Aflatoxin
www.medicalnewstoday.com
A new study has found that chlorophyll and its derivative chlorophyllin are effective in limiting the absorption of aflatoxin in humans. Aflatoxin is produced by a fungus that is a contaminant of grains including corn, peanuts and soybeans; it is known to cause liver cancer - and can work in concert with other health concerns, such as hepatitis.
Levels of aflatoxin are carefully regulated in the United States, but are often found in the food supplies of developing nations, especially those with poor storage facilities.
OSU scientist George Bailey, a distinguished professor of environmental and molecular toxicology, pioneered studies of aflatoxin in China, where he found that in one region, one out of every 10 adults died from liver cancer.
But what has the science world particularly intrigued with this follow-up study is the methodology used by the researchers - a new "Phase 0" approach that safely tests low levels of carcinogens in human volunteers to measure the total aflatoxin exposure and to determine the effect of dietary chlorophlls on reducing this exposure.
Results of the study were just published in the journal Cancer Prevention Research.
Bailey and several other researchers, including lead author Carole Jubert, were part of the recent study. The journal also included a perspective written by a pair of Johns Hopkins researchers - Thomas Kensler and John Groopman - who praise the methodology and suggest that these Phase 0 "microdosing" studies should be expanded.
They wrote: "…microdosing studies with carcinogens have the potential to provide important insights into chemopreventive interventions and to enhance the overall clinical development and safety evaluation of preventive agents."
The Phase 0 study "…may open the door for all kinds of new research," said Jubert, a former researcher in Bailey's lab at OSU's Linus Pauling Institute. Jubert now works for Life Microsystems, an OSU spinoff company that hopes to continue work with natural products grown in Oregon, including pure chlorophylls.
"The technology is not particularly difficult," she added. "It's just a novel approach to evaluate toxin exposure in humans."
In their study, Jubert and her colleagues gave very low doses of aflatoxin labeled with carbon-14 isotopes as a tracer to four human volunteers. They then gave the volunteers the same doses of aflatoxin along with doses of either chlorophyll or chlorophyllin, which previously had been shown to reduce carcinogen bioavailability in trout and rats. Using an accelerator mass spectrometer, they measured the rate of aflaxtoxin bioavailability. This technique is extremely sensitive, the researchers say, allowing measurement of minute amounts of any labeled compound.
Their research revealed rapid absorption of aflatoxin, which was significantly limited after the chlorophyll and chlorophyllin treatments.
"The beauty of this kind of 'Phase 0' study is the use of ultra-sensitive technology and 'microdoses' of environmental carcinogens to study toxicokinetics within the human body," said John Mata, an OSU pharmacologist and second author on the study. "These measurements can be important because they allow us to better design future studies to understand the effects of dietary constituents on cancer risk.
"In this case, clearly the results merit further study," Mata added. "We showed that aflatoxin is absorbed quite rapidly and that chlorophyll and chlorophyllin have an ameliorating effect, preventing the toxin from getting into the bloodstream. Further studies can more precisely explore the interactions, as well as dosage levels."
Jubert and Mata also have tested the feasibility of using similar technology on human exposure to other toxins, including smokers who ingest carcinogens through cigarette smoke.
Mata, a professor in OSU's College of Veterinary Medicine, is a pharmacologist who previously worked in the drug industry. He said Phase 1 studies are designed to see if a compound is safe; Phase 2 expands the scope of the project, and Phase 3 looks at the compounds' efficacy. Phase 0 represents a new concept - a way to measure the kinetics of a drug by using extremely small doses that pose little risk to the volunteers.
In this case, the amount of radiation given the human volunteers was equal to that you would encounter from a one-hour airplane ride; the level of aflatoxin administered was 1/30th the amount the Food and Drug Administration allows in a peanut butter sandwich.
Source: Oregon State University
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January 4, 2010
Experts Praise Scheme to Tackle Hepatitis C
http://www.theboltonnews.co.uk
A SCHEME tackling a serious blood disease has won praise from health experts.
Work in Bolton, and Greater Manchester to combat hepatitis C has been highlighted by the Health Protection Agency.
The association of Greater Manchester PCTS has funded a strategy to tackle the infection and the work includes a campaign called What Did You Do Back In The Day? Run in partnership with Rock Radio, it encourages people to think if they have put themselves at risk and get checked out.
There was a 200 per cent increase in the number of online and telephone enquiries about being tested. Drug workers in Bolton and across Greater Manchester have also been trained to use a finger prick test to identify hepatitis C sufferers and between April and December 2009, 140 tests were carried out in the town.
The HPA national report, Hepatitis C in the UK: 2009 Report, highlights the Greater Manchester scheme and says: “Governments, the NHS and the voluntary sector have all developed initiatives. It is hoped these will help reduce the levels of undiagnosed infection, and help individuals access treatment and care.”
The campaign will continue, targeting GP practices to help highlight the infection, with a event planned for the county in February.
There will also be a Back in The Day event in May and a day for drug workers in Bolton will be held later in the year.
Latest figures from the HPA show there are 1,679 reported new cases of hepatitis C in the North West — higher than anywhere else in the UK and infection rates continue to rise.
There are around 1,500 people affected in Bolton, with 20,000 across the county and around 185,000 in the UK. Hepatitis C is a viral infection which causes swelling or inflammation of the liver.
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Head-to-Head Studies Identify Best Treatment Regimen for Hep C
www.eurekalert.org
Peginterferon alpha-2a may yield higher response rate than peginterferon alpha-2b
In patients with chronic hepatitis C, treatment with peginterferon alpha-2a (PegIFNα2a) plus ribavirin (RBV) better suppresses the virus to undetectable levels in the blood than treatment with peginterferon alpha-2b (PegIFNα2b) plus RBV, according to two new head-to-head studies in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute.
Patients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of peginterferon, either PegIFNα2a or PegIFNα2b, and RBV. In fact, this combination, which is the treatment of choice, has increased sustained virological response (SVR) rates from less than 20 percent to more than 60 percent. Obtaining complete SVR is the goal of treatment for HCV; patients who experience SVR for more than six months often do not experience disease relapse.
While previous trials have demonstrated that both pegylated interferons are effective and safe when administered with RBV, only two randomized clinical studies have compared the efficacy of the peginterferon formulations, neither of which was sufficiently powered to detect a statistically significant difference in SVR rates.
"Head-to-head trials comparing the efficacy and safety of PegIFNα2a or PegIFNα2b in combination with RBV in the treatment of patients with chronic hepatitis C are needed," said Massimo Colombo, MD, of the University of Milan and author of one of the head-to-head studies published in Gastroenterology. "There is insufficient evidence to support conclusions that one therapeutic regimen is superior to the other one."
In the first study, previously untreated patients with chronic hepatitis C were randomly assigned after stratification for HCV genotype to either RBV combined with PegIFNα2a or PegIFNα2b for 24 or 48 weeks, according to virus genotype. Researchers found that overall, the SVR rate was significantly higher in PegIFNα2a than in PegIFNα2b (66 percent versus 54 percent).
"Whether our strategy of RBV dosing, which is at variance with the standard of care for PegIFNα2a treatment, is indeed cost-effective, needs to be prospectively assessed through a pharmaco-economy study," added Dr. Colombo.
Similar results were reported in a second study published in Gastroenterology. In this single-center, randomized, head-to-head study, 320 consecutive, treatment-naïve, HCV-RNA-positive patients with chronic hepatitis were randomly assigned to groups given once-weekly subcutaneous PegIFNα2a or PegIFNα2b plus RBV 1,000 mg/day or 1,200 mg/day for 48 weeks or 24 weeks. More patients in the PegIFNα2a group than the PegIFNα2b group achieved SVR (68.8 percent versus 54.4 percent).
In fact, study authors found that in patients with chronic HCV infection, treatment with PegIFNα2a plus RBV produced a significantly higher SVR rate than treatment with PegIFNα2b plus RBV; the safety profile of the two regimens were similar.
"The fact that both of these studies yielded similar and significant results confirms the potential advantages of PegIFNα2a plus RBV versus PegIFNα2b plus RBV," said Antonio Ascione, MD, of Fatebenefratelli Hospital in Naples and lead author of this study. "These advantages may translate to the development of promising new direct anti-viral drugs against HCV."
For more information on viral hepatitis, visit the AGA patient center at www.gastro.org/patient.
About the AGA Institute
The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org.
About Gastroenterology
Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, CABS, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit www.gastrojournal.org.
i Rumi M et al. Randomized Study of Peginterferon-α2a Plus Ribavirin vs Peginterferon-α2b Plus Ribavirin in Chronic Hepatitis C. Gastroenterol 2010;138:108-115.
ii Ascione A et al. Peginterferon Alpha-2a Plus Ribavirin Is More Effective Than Peginterferon Alpha-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection. Gastroentrol 2010;138:116-122.
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January 5, 2010
Hepatitis C Treatment Effective in Injection Drug Users Study Finds Treatment Effective Even among Patients Co-Infected with HIV
http://www.modernmedicine.com
MONDAY, Jan. 4 (HealthDay News) -- Treatment of recent hepatitis C virus (HCV) infection is effective in injection drug users, even those co-infected with HIV, according to a study in the January issue of Gastroenterology.
Gregory J. Dore, M.D., from the University of New South Wales in Sydney, Australia, and colleagues analyzed data from a clinical trial of 109 patients recently infected with HCV treated with pegylated interferon-alfa-2a (74 patients) or pegylated interferon-alfa-2a plus ribavirin if co-infected with HIV (35 patients). Of these, 79 percent had injected drugs in the past six months.
The researchers found that, in patients infected with HCV only, the sustained virologic response rate was 55 percent by intention-to-treat analysis and 72 percent by per-protocol analysis. In patients co-infected with HIV, the response rate was 74 percent by intention-to-treat analysis and 75 percent by per-protocol analysis. After accounting for possible confounding factors, decreased social functioning and current opiate pharmacotherapy were associated with lower responses. Adherence was associated with higher response rates (63 versus 29 percent).
"This study found that treatment for recent HCV infection is effective in people whose infection was acquired through injection drug use, even in those with HIV co-infection," Dore and colleagues conclude. "Strategies to engage socially marginalized individuals and increase adherence should improve treatment outcomes in this population."
Several authors reported financial, consulting, or advisory relationships with pharmaceutical companies.
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Lower CD4 Count Predicts Slow HCV Decline and Poor Response to Pegylated Interferon plus Ribavirin in HIV/HCV Coinfected People
www.hivandhepatitis.com
By Liz Highleyman
SUMMARY: HIV/HCV coinfected patients experienced a smaller decrease in HCV RNA than HCV monoinfected individuals during the first-phase of decline after starting interferon-based therapy, and among coinfected patients, those with lower CD4 cell counts had slower HCV decline. These results, published in the December 2009 Journal of Acquired Immune Deficiency Syndromes, suggest that immune status plays an important role in treatment response.
Past research has shown that HIV/HCV coinfected people tend to experience more rapid liver disease progression and do not respond as well to interferon-based therapy as those with HCV alone. However, some evidence indicates that coinfected patients with well-preserved immune function may fare nearly as well as HCV monoinfected individuals.
To further explore this issue, Avidan Neumann from Bar-Ilan University in Israel and colleagues assessed the influence of CD4 T-cell count on HCV viral kinetics -- or pattern of change -- and treatment outcomes in coinfected patients.
The investigators compared HCV viral load kinetics among 32 HIV/HCV coinfected study participants and 12 HCV monoinfected patients treated with 1.5 mcg/kg/week pegylated-interferon alfa-2b (PegIntron) plus 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks.
Results
- Having a baseline CD4 count >450 cells/mm3 was significantly associated with sustained virological response (SVR) in coinfected genotype 1 patients (P < 0.002).
- First-phase HCV RNA decline was significantly less among coinfected patients with low as compared with high CD4 counts (P < 0.03).
- First-phase HCV decline was also reduced among HIV/HCV coinfected compared with HCV monoinfected individuals (P < 0.002).
- The slope of second-phase HCV decline showed a similar trend for coinfected patients.
Based on these findings, the researchers concluded, "Low baseline CD4+ T-cell count is associated with slower HCV viral kinetics and worse response to treatment among HIV coinfected patients, suggesting HCV treatment response depends on immune status."
"HCV genotype 1 coinfected patients have slower first phase viral kinetics than HCV monoinfected patients," they continued. "First phase viral decline (> 1.0 log) and second phase viral decline slope (> 0.3 log/week) are excellent predictors of SVR for coinfected patients."
Bar-Ilan University, Ramat-Gan, Israel.
Reference
NU Avidan [aka Neumann AU], D Goldstein, L Rozenberg, and others. Hepatitis C Viral Kinetics During Treatment With Peg IFN-alpha-2b in HIV/HCV Coinfected Patients as a Function of Baseline CD4+ T-Cell Counts. Journal of Acquired Immune Deficiency Syndromes 52(4): 452-458 (Abstract). December 2009.
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Natural Compound Blocks Hepatitis C Infection: Finding May Lead to a New Treatment
www.eurekalert.org
Researchers have identified two cellular proteins that are important factors in hepatitis C virus infection, a finding that may result in the approval of new and less toxic treatments for the disease, which can lead to liver cancer and cirrhosis.
An estimated 270 to 300 million people worldwide are infected with hepatitis C and the conventional treatments – interferon and ribavirin – can have significant side effects. A new drug targeting cellular proteins rather than viral proteins would be a valuable addition to the treatment arsenal, said Samuel French, an assistant professor of pathology and senior author of the study.
French and his team set out to identify the cellular factors involved in hepatitis C replication and, using mass spectrometry, found that heat shock proteins (HSPs) 40 and 70 were important for viral infection. HSP 70 was previously known to be involved, but HSP 40 was linked for the first time to hepatitis C infection, French said. They further showed that the natural compound Quercetin, which inhibits the synthesis of these proteins, significantly inhibits viral infection in tissue culture.
"This is an important finding because we can block these proteins with the idea of reducing the level of the virus in people and, ideally, completely eliminate it," said French, who also is a researcher at UCLA's Jonsson Comprehensive Cancer Center.
The study appeared in the most recent issue of the journal Hepatology.
Since Quercetin has been shown to inhibit hepatitis C infection, French said, a Phase I clinical trial will be launched at UCLA to determine if the compound is safe and effective.
Quercetin is a plant-derived bioflavonoid, and is used by some people as a nutritional supplement. Laboratory studies show it may have anti-inflammatory and antioxidant properties, and it is being investigated for a wide range of potential health benefits. Currently, there are early-stage clinical trials testing quercetin for safety and efficacy against sarcoidosis, asthma and glucose absorption in obesity and diabetes.
"Because Quercetin targets cellular proteins rather than viral proteins, there is less likelihood of developing viral resistance," French said. "Cellular proteins cannot change like viral proteins can."
Many patients in the United States have a type of hepatitis C virus that does not respond to the standard treatments. In these cases, if the virus can't be blocked, end-stage liver disease and, ultimately, death may occur. Once HSP 40 and 70 were identified, French and his team used Quercetin in an attempt to block the proteins and found that the compound "reduced infectious particle production at non-toxic concentrations," according to the study.
"Quercetin may allow for the dissection of the viral life cycle and has potential therapeutic use to reduce virus production with low associated toxicity," the study states.
The UCLA clinical trial will most likely target those with type 1 hepatitis C, which is the non-responsive type prevalent in this country. Only about 50 percent of those with type 1 hepatitis C respond to treatment, French said.
Volunteers with type 1 hepatitis C who opt not to undergo conventional therapies would be recruited for the study. In other studies in other diseases, Quercetin has resulted in no significant side effects, French said.
"A non-toxic treatment for chronic hepatitis C would be great because our current therapies have significant side effects and only a certain percentage of the patient population responds," French said.
The three-year study was funded by the National Institutes of Health, the Cure Digestive Diseases Research Center and the Stein Oppenheimer Endowment Award.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2009, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
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Liver Stiffness Measurements Identify Patients with Rapid or Slow Fibrosis
www.eurekalert.org
Life-saving therapeutic interventions possible with early detection of hepatitis C recurrence
A recent study by doctors from the Hospital Clínic in Barcelona, Spain determined that repeated liver stiffness measurements (LSM) in the first year following liver transplant (LT) could discriminate between slow and rapid "fibrosers" (patients with fibrosis stage of F2-F4 one year post LT). LSM were extremely accurate, particularly at the 6-month post LT point, in detecting severity of fibrosis. Determining those at risk for a recurrence of hepatitis C virus (HCV) allows for early-stage administration of therapies that could prevent LT or graft failure. The full findings are published in the January 2010 issue of Hepatology, a journal of the American Association for the Study of Liver Diseases
From August 2004 to January 2008, 84 LT patients with HCV recurrence and 19 patients transplanted for reasons other than HCV were included in the study led by Miquel Navasa, M.D. The cause of LT in the non-HCV control group included: alcoholic cirrhosis (n=10), primary biliary cirrhosis (n=2), Caroli's disease (n=2), familial amyloid polyneuropathy (n=2), autoimmune hepatitis (n=1) and cryptogenetic cirrhosis (n=2). Liver stiffness was measured using Fibroscan® on the right lobe of the liver with repeated measurements during the first year after LT.
Results indicate that LSM did not significantly increase during the first year after LT for all control participants. There were 53 patients deemed slow "fibrosers" with median LSM at 3, 6, 9, and 12 months at 6.9, 6.9, 7.5, and 6.6 kilopascals (kPa-a standard unit of pressure), respectively, without significant increase during the follow-up year. The remaining 31 participants were rapid "fibrosers" who had median LSM at months 3, 6, 9, and 12 of 7.5, 9.9, 9.5 and 12.1 kPa, respectively. "Our study clearly shows two different speeds of liver fibrosis progression during the first year after LT," said Dr. Navasa. "Slow "fibrosers" progressed at the same rate as non-HCV LT patients, while rapid "fibrosers" showed significant fibrosis and portal hypertension very early in the follow-up."
Researchers also conducted univariate and multivariate analyses to identify the variables associated with the presence of significant fibrosis (F≥2) one year post LT. The univariate analysis identified 6 variables associated with rapid fibrosis progression: Cytomegalovirus infection, ALT level, bilirubin level and HCV-viral load (at three months), bilirubin level and LSM (at six months). The multivariate analysis showed that only two variables at six months were independent predictors of fibrosis: LSM and bilirubin level. "Using non-invasive detections such as LSM or bilirubin levels at 6 months can accurately predict the risk to develop significant fibrosis in LT patients, concluded Dr. Navasa. "Our results will need to be validated by other transplant centers, but we believe these models could be widely used in clinical practice to adopt appropriate therapeutic interventions at first signs of HCV recurrence.
In the U.S. the Organ Procurement and Transplantation Network (OPTN) recorded that 4,747 Americans underwent LTs during 2009. According to a report by the Scientific Registry of Transplant Recipients (SRTR), the graft and patient survival rates were 82.4% and 87.1% respectively for deceased donor LTs and 84.8% and 89.9% respectively for living donor LTs. These statistics are based on transplants conducted between 2005 and 2006. Past studies have shown a recurrence of HCV is the first cause of graft loss and reduction in patient survival in most liver transplant programs.
Article:
"Liver Stiffness Identifies Two Different Patterns of Fibrosis Progression in Patients with HCV Recurrence after Liver Transplantation." José A. Carrión, Ferran Torres, Gonzalo Crespo, Rosa Miquel, Juan-Carlos García-Valdecasas, Miquel Navasa and Xavier Forns. Hepatology; Published Online: October 18, 2009 (DOI:10.1002/hep.23240); Print Issue Date: January 2010 http://www3.interscience.wiley.com
/journal/122653627/abstract
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://www3.interscience.wiley.com/
journal/106570044/home.
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
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Factors that Predict Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis B Patients
www.hivandhepatitis.com
By Liz Highleyman
SUMMARY: HBV genotype, HBV DNA (viral load), and alanine aminotransferase (ALT) level are predictors of sustained response to pegylated interferon for treatment of chronic hepatitis B, according to study results reported in the December 2009 issue of Gastroenterology.
Chronic hepatitis B virus (HBV) infection is treated with either directly-targeted antiviral agents -- such as lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), or tenofovir (Viread) -- or with conventional or pegylated interferon alfa, which works by stimulating the body's immune response against the virus.
However, pegylated interferon produces a sustained response in only a minority of patients and causes considerable side effects, the study authors noted. Therefore, it would be useful to be able to predict in advance who is likely to respond.
The investigators analyzed data from 2 large international trials of hepatitis B "e" antigen (HBeAg) positive chronic hepatitis B patients to determine which ones were most likely to respond to pegylated interferon.
The study included 542 participants treated with 180 mcg/week pegylated interferon alpha-2a (Pegasys) for 48 weeks, and 266 patients treated with 100 mcg/week pegylated interferon alpha-2b (PegIntron) for 52 weeks. A total of 87 participants were excluded for various reasons, leaving 721 patients in the final analysis.
Sustained response was defined as HBeAg loss and HBV DNA < 2.0 x 10(4) IU/mL at 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response.
Results
The following factors were significant predictors of sustained response:
- HBV genotype;
- High ALT level (>2 x upper limit of normal);
- Low HBV DNA level (< 2.0 x 10(8) IU/mL),
- Female sex;
- Older age;
- Lack of previous interferon therapy (i.e., treatment-nave).
- The strongest predictors were high ALT in genotype B patients, and low HBV DNA in genotype C patients.
- Genotype A patients with high ALT and/or low HBV DNA had > 30% predicted probability of sustained response.
- Genotype D patients, however, had a low probability of sustained response regardless of ALT or HBV DNA levels.
"The best candidates for a sustained response to [pegylated interferon alfa] were genotype A patients with high levels of ALT or low levels of HBV DNA and genotype B and C patients that have both high levels of ALT and low HBV DNA," the investigators concluded. "Genotype D patients have a low chance of sustained response."
With the licensing of pegylated interferon alfa-2a and 5 nucleoside/nucleotide analogs for the treatment of chronic hepatitis B, "the choice of antiviral therapy has become more important and more complex at the same time," the study authors elaborated in their discussion. "Because both treatment with interferon-based therapy and [nucleoside/nucleotide analog] therapy have proven effective and can improve long-term outcome, the pros and cons of these drugs as well as patient-specific characteristics should be taken into consideration."
All major practice guidelines have advocated interferon-based therapy as potential first-line treatment for both HBeAg positive and HBeAg negative patients, since sustained response and hepatitis B surface antigen (HBsAg) loss seem to occur more often with interferon than with directly targeted antiviral agents, they noted. However, the use of pegylated interferon currently accounts for no more than 10% of all prescriptions for chronic hepatitis B treatment.
"The relatively low use of [pegylated interferon] may be explained by its significant side effects and need for administration by injection. Furthermore, recommendations on the use of [pegylated interferon] in specific subsets of patients who are most likely to have a sustained response and HBsAg seroconversion were lacking," the researchers continued. "When we are able to identify patients with a high likelihood of response to [pegylated interferon], the proportion of patients achieving sustained response after treatment with this drug probably can be increased."
Department of Gastroenterology & Hepatology, Department of Epidemiology & Biostatistics, and Department of Public Health, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China; Department of Medicine, Songklanakarin Hospital, Songkla, Thailand; Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Reference
E Buster, BE Hansen, GK Lau, and others. Factors that Predict Response of Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B to Peginterferon-alpha. Gastroenterology 137(6): 2002-2009 (Abstract). December 2009.
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January 6, 2010
How Is Hepatitis B Managed in a Patient with Acute Intermittent Porphyria?
www.medscape.com
David Bernstein, MD
Question
What is the appropriate treatment for a patient with acute intermittent porphyria and hepatitis B (e-antigen negative) with a normal alanine transaminase and a hepatitis B virus viral load of 45,000 copies/mL (log 4.56)?
Response
Acute intermittent porphyria has not been associated with hepatitis B. Therefore, the question regarding treating the aforementioned patient centers on the patient's hepatitis B status. The patient described previously has a pre-core mutant with normal liver enzymes and detectable virus.
The first decision point is to determine whether this patient has cirrhosis. If the patient is cirrhotic, as evidenced by thrombocytopenia and splenomegaly or other signs of portal hypertension, I would recommend initiating hepatitis B therapy with an oral agent. Pegylated interferon is not to be used in patients with hepatitis B and cirrhosis.
If the patient does not have obvious cirrhosis, then I would recommend following the guidelines published by Keeffe and colleagues.[1] These guidelines recommend either monitoring the alanine transaminase and hepatitis B virus -DNA periodically or performing a liver biopsy to evaluate for underlying fibrosis and initiating treatment if the biopsy reveals significant fibrosis.
I will usually observe these patients for a 6-month period of time, and if the parameters remain unchanged, I proceed with a liver biopsy.
David Bernstein, MD, is Chief, Digestive Disease Institute, North Shore University Hospital-Long Island Jewish Medical Center, Manhasset, New York; Associate Professor of Medicine, New York University School of Medicine, New York, NY
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Fiorito: Ottawa Puts Monkey on Pot User's Back
http://www.thestar.com
By Joe Fiorito, City Columnist
You know how it would go if you were into your dealer for five grand. Here's what happens when your dealer is the Government of Canada:
You remember Jim Meeks. He was one of those who went out with a camera a while back, taking photos of the places where the homeless sleep.
He did not need a guide. He is familiar with the undersides of bridges, with ravines and sidewalk grates, and with the granite interstices between the tall cold buildings of the downtown core.
He now lives in a room near Seaton House. His building is rough, but his place is snug.
Jim also has a medical marijuana card, the source of his most pressing problem, and the inspiration for today's column.
He said, "I'm on disability." In fact, his disability is plural. "I have epilepsy. I have irritable bowel syndrome, and I have back damage from life on the street, and from beatings."
Yikes.
"The epilepsy? I've had it most of my life, but I haven't had a grand mal seizure in 20 years." Does he have petit mal seizures? "My kids say I have them. I sometimes sort of stare off with my mouth open. My granddaughter calls it 'Grandpa's banjo face.'"
He mugs for me.
She is not wrong.
"My doctor found out I smoked pot, and he did a brain scan. Turns out I am stable when I have pot. When I don't, I'm not stable."
I said his health problems were multiple. Take a deep breath: He also has hepatitis C, and he had a quadruple bypass in 2001.
The marijuana helps with the fatigue, the nausea and lack of appetite that accompany hep C. But who smokes dope after a bypass?
"The doctor said I couldn't quote him, but marijuana has an antispasmodic agent. He said I just shouldn't smoke tobacco."
Jim was able to get a medical marijuana card. He's had it for a few years, and orders pot by mail from Saskatchewan. "You send away for it and they bill you." That beats buying weed on the street.
So what's the problem?
"It isn't covered by OHIP, and I'm on social assistance, so I can't claim it on my taxes."
Let's do the math:
He uses four grams a day; that's 120 grams a month. Civil service dope costs five bucks a gram, which means Jim's costs are $600 a month for a drug prescribed by his doctor to control his seizures and his spastic colon, and to minimize the fatigue and the loss of appetite and other ailments.
The cost is not covered, and his income is minimal. He gets $250 a month from a pension, he earns $100 a month from his volunteer work, and he gets $480 from his disability pension. His apartment costs $139 a month.
At this stage, he has run up a tab of five grand with Health Canada. He isn't trying to shirk. "I called them. I said I was on social assistance. They said they'd make the repayments as low as they could. I'm sending them $105 a month."
That's money he doesn't have for medicine he needs, and for which he has a prescription.
Too bad he's not rich.
What now? "I'll have to order less. I have a lot of anxiety over what will happen."
Here's what I don't get: If he needs the stuff for his health, and if it is legal and prescribed, why is it not affordable?
You know what I'm going to say now. A dealer would break your legs if you owed five grand for dope bought on the street.
Health Canada?
They just hamstring you.
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Could a Patient in Iowa Have Hepatitis E?
www.medscape.com
William F. Balistreri, MD
Question
A renal transplantation patient from Iowa has developed persistent unexplained hepatitis. Could this be caused by hepatitis E virus (HEV)?
Response
Yes, hepatitis E virus (HEV) -- an established cause of outbreaks of waterborne acute hepatitis in tropical and subtropical countries -- is rarely considered to be associated with outbreaks or sporadic cases of viral hepatitis in industrialized countries. However, emerging data suggest that HEV clearly causes acute (and perhaps even chronic) hepatitis worldwide. More than 140 articles related to HEV were published in 2009.
What Is HEV?
HEV is a small, nonenveloped particle that consists of a polyadenylated single-strand RNA molecule; it is the sole member of the genus Hepevirus in the family Hepeviridae. HEV is transmitted predominantly by the fecal-oral route and typically causes self-limited acute hepatitis. Infection can be severe -- death rates among young adults and pregnant women are 0.5%-3% and 15%-20%, respectively. Identification and characterization of swine HEV in many countries and the close relationship of swine HEV to locally characterized human HEV suggest that HEV is a zoonotic virus and that there are domestic swine and wild deer reservoirs of HEV in nature.
Does HEV Occur in the United States?
The epidemiology of HEV in the United States was recently reported by Kuniholm and associates[3] who used an enzyme immunoassay to measure anti-HEV immunoglobulin (Ig) G antibodies in 18,695 serum samples collected for the Third National Health and Nutrition Examination Survey. The calculated estimate of HEV seroprevalence in the civilian noninstitutionalized US population who reported no travel history was 21% (95% confidence interval, 19%-23%). Among US-born individuals, men, non-Hispanic whites, and persons residing in the Midwest and/or in metropolitan areas had the highest seroprevalence estimates. Having a pet in the home and consuming liver or other organ meats more than once per month were significantly associated with increased odds of HEV seropositivity. Thus, although exposure to HEV is common in the United States, hepatitis E is rarely reported.
Other recent outbreaks.
Among the many outbreaks and sporadic cases described in the recent literature, several are of special interest because they reflect the epidemiology and significance of HEV. A recent outbreak of hepatitis E occurred among cruise ship passengers. After receiving reports of cases of acute hepatitis E among returning cruise ship passengers, the UK Health Protection Agency surveyed passengers who had traveled for any part of the same 3-month cruise in 2008. Among 789 passengers, 4% were anti-HEV IgM- and IgG-positive, suggesting recent acute infection, and 21% were IgG-positive only, indicating past infection. HEV RNA sequences were identical, suggesting a common source. Of the 33 passengers who had serologic evidence of recent HEV infection, 11 had symptomatic hepatitis. In a multivariate analysis, factors associated with HEV infection included being male, drinking alcohol, and eating shellfish. The investigators concluded that the most likely source was food eaten on board the ship.
During 2 multiyear outbreaks of acute viral hepatitis identified in Uzbekistan, HEV was associated with high mortality in pregnant women and in children younger than 3 years of age. Increased severity has also been noted in patients coinfected with HEV and other hepatotropic viruses (including HIV). Zaki and colleagues studied 162 children who had sporadic acute hepatitis and detected anti-HEV in 57% of children with HBV, 52% of HCV-infected patients, 34% of children with HAV infection, and 7% of patients who had "non- A,B,C hepatitis." The prevalence of anti-HEV IgG and IgM correlated with the levels of aspartate and alanine transaminase and outcomes compared with patients who had acute hepatitis as a result of A and C viruses alone.
HEV and Chronic Hepatitis in Organ-Transplant Recipients
Although HEV infection induces self-limiting liver disease in immunocompetent persons, chronic hepatitis E has recently been identified in immune- suppressed organ transplant recipients. Kamar and associates identified 14 cases of acute HEV infection in patients who received organ transplants. HEV RNA was detected in the serum of each of these patients. Chronic hepatitis developed in 8 of the patients. Gerolami and colleagues reported a case in which chronic HEV infection induced rapid and severe cirrhosis. Several subsequent reports suggest that organ recipients who have enigmatic hepatitis be tested for HEV.
HEV Vaccine
A cell culture system for the propagation of the virus has been described, and a very successful phase 2 vaccine trial has been completed. Shrestha and associates evaluated the safety and efficacy of an HEV recombinant protein vaccine in a phase 2, randomized, double-blind, placebo-controlled trial in Nepal. The vaccine efficacy was 95.5% (95% confidence interval, 85.6-98.6). Thus, in a high-risk population, HEV vaccine may be an effective method to prevent hepatitis E.
Bottom Line
HEV does, indeed, infect patients worldwide and can be associated with significant disease, especially in immune-compromised individuals. Increased surveillance and screening is recommended, even in Iowa.
William F. Balistreri, MD, Dorothy M. M. Kersten Professor of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Medical Director, Liver Transplantation Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
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Mental Health and Addiction Equity: New Updates, Long Overdue
www.huffingtonpost.com
Dr. Gabor Mate
The new guidelines for the Mental Health Parity Act (MPHA) went into effect on January 1, 2010, arriving not a moment too soon. Federal law now requires that insurers who cover mental health or addiction treatment must do so equally with the coverage they provide for medical and surgical ailments.
State and federal governments in the United States currently spend more than $15 billion per year, and insurers at least another $5 billion per year, on substance-abuse services for some four million people, but researchers estimate that some twenty million Americans who could benefit from treatment are not getting it. As the psychologist Peter Levine notes, "The costs in human suffering, family disintegration, and lost productivity are staggering." Not to provide treatment is to condemn people to a lifetime of misery and, with distressing frequency, to untimely death.
The MPHA implicitly recognizes that addiction is a mental health issue and that its consequences can be as debilitating as that of any chronic, severe physical illness – in fact, physical illness is often the outcome of untreated addiction. HIV, Hepatitis C, multiple infections of body organs from liver to heart to brain are the frequent consequences of injection drug use, just as lung cancer and chronic lung disease follow from nicotine addiction and cirrhosis of the liver and many other diseases occur in the wake of chronic alcoholism. So any distinction between addiction and physical illness is artificial.
It is also clear that addiction itself is a disease of the brain. Through new imaging methods we've been able to glimpse the human brain in action under the immediate influence of drugs and after long-term drug use. The findings are abnormal, and they get more abnormal with chronic use. Those who study addiction agree that on the basic physiological level, addiction represents "a different state of the brain," in the words of physician and researcher Charles O'Brien. The addicted brain just doesn't function normally, any more than a diseased heart functions normally. The central dilemma is that this dysfunctional organ now has to make a decision to heal itself. It can rarely do so without expert help and compassionate support.
Addiction, contrary to popular opinion, is not a simple matter of a poor lifestyle "choices," bad decisions, or moral failure. Large scale population studies have shown that most severely addicted people suffered extreme adversity in childhood – neglect, abuse, trauma that most of us cannot even imagine. The brain is shaped by such influences. The brain circuits that later become implicated in addiction are potentiated to do so by what happens in early childhood. As a physician working with a highly addicted population at a residential harm reduction center, I can report, for example, that among my female patients there is not one who was not sexually abused in childhood – as were many of the men.
Finally, there is a close link between addiction and mental health problems, since all addictions are ill-fated attempts at self-medication. What conditions do people self-medicate? Post-Traumatic Stress Disorder, for example, with opiates and other drugs; ADHD, with stimulants. Depression, anxiety, social phobias are also among the mental health disorders people try to soothe through drug use.
The updated guidelines to the Mental Health Parity Act will not have universal reach, nor will it be the final answer to the many gaps in addiction treatment in the U.S., but it is an important step in the right direction.
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January 7, 2010
Liver Donations from Living Donors Increase 42% after Educational Intervention
Wiley-Blackwell
Living Liver Donors Share Their Stories – More Step Forward to Donate
A recent study found that living donation increased 42% and the number of individuals who presented for donation evaluation increased 74% at centers in New York. The surge in live donation and donor evaluation occurred after additional education was provided to liver transplant candidates. Those candidates exposed to the peer-based intervention (education) reported significantly greater knowledge, greater likelihood to discuss donation and increased self-efficacy compared to those not exposed to the intervention. Details of the study are reported in the January 2010 issue of Liver Transplantation, a journal of the American Association for the Study of Liver Diseases, published by Wiley-Blackwell.
According to the United Network for Organ Sharing (UNOS) as of January 30, 2009 there were 100,539 candidates on the waiting list in the U.S., with over 15,000 individuals in need of a liver transplant. UNOS also reported the number of deceased donors is decreasing from 6,650 donors in 2006 to 6,494 donors in 2007—a concerning fact for liver transplant candidates. Past studies have shown that the median wait time for a liver was 296 and 306 days (2005 and 2006, respectively). In New York State in 2008, there were 133 deaths on the liver waitlist, an increase of 16% over 2007. The critical shortage of deceased liver donors, a lack of broader national sharing, increased wait times and deaths on the wait list, all incentivize transplant programs to look to alternative ways to expand the pool of livers available for transplant.
At the time of the study and based on UNOS data, New York had 1,947 individuals on the liver wait list which represents 12% of candidates nationally. In 2006-2007, random samples of waitlisted candidates at five transplant centers in New York were selected to complete (pre-intervention) surveys. A second sample of waitlisted candidates completed post-intervention surveys in 2008. These surveys included questions about: length of time on waiting list, education level, ethnicity, age, if they received educational materials (and helpfulness of materials), if they had discussed living liver donation with loved ones and if they had any plans to do so and where else they may have learned about liver transplantation.
“Past studies have show waitlisted candidates concerns over donor safety coupled with their general lack of knowledge about organ donation created a reluctance on the part of candidates to discuss living donor liver transplantation (LDLT) with family and friends,” said Samantha DeLair, Director, New York Center for Liver Transplantation and lead author of this study. “The intervention material we used included testimonials and self-report data from living donors to educate liver candidates about the impacts, both the positives and the challenges of living liver donation,” added Ms. DeLair.
In New York all living liver donors are periodically surveyed to assess the individuals’ health and quality of life post-donation. Educational material used in the study to educate liver candidates was derived from 44 survey respondents in 2004-2005. The content of the booklet and DVD focuses on donor responses regarding: the surgery, recovery after donation, costs of donation, employment issues, and life after donation. The educational material used in this study, “In Their Own Words – The Experiences of Living Liver Donors,” may be accessed at www.nyclt.org/living_donor/.
Of the donors whose self-reports were used to create the educational material, 87% recommend seeking input of a former donor prior to donating. One anonymous donor gives this advice to individuals considering the option of LDLT, “Every decision is personal…get as much information as possible and speak to other donors.”
There were 437 waitlisted candidates at pre-test who completed surveys and 338 individuals at post-test. Participants had a median age of 55 years with 63% male and 56% of the total sample was White, non-Hispanic. Most surveyed were either newly listed (26%) or had been on the list for greater than 1 year (50%). For those participants exposed to the educational intervention, 91% reported having a “fair amount” or “a lot” of knowledge regarding LDTL compared to 70% of the unexposed group.
This study also tracked the number of friends and family members who presented to the five transplant centers for further information, discussion, and if appropriate, comprehensive evaluation for LDLT. Results indicate there was a 74% increase in LDLT evaluations from 2006 to 2008 at the intervention sites. After the educational intervention, there was a 42% increase in the number of individuals who completed an evaluation and donated a liver graft.
“Our data is compelling given the gains in waitlist candidates’ knowledge of LDLT and the increases in the number of individuals interested in using this transplantation procedure,” concluded Ms. DeLair. “It is important to follow live donors post-donation both for the donors themselves and to provide waitlist patients and their loved ones with as much information as possible as they consider live donation for themselves.”
Article:
“A Peer-Based Intervention to Educate Liver Transplant Candidates about Living Liver Donation.” Samantha DeLair, Thomas Hugh Feeley, Hyunjung Kim, Juan del Rio Martin, Leona Kim-Schluger, Dianne LaPointe Rudow, Mark Orloff, Patricia A. Sheiner, Lewis Teperman. Liver Transplantation; Published Online: December 30, 2009 (DOI10.1002/lt.21937); Print Issue Date: January 2010 http://www3.interscience.wiley.com
/journal/123226251/abstract
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OraSure Technologies Files Additional Data with FDA in Support of PMA Application for OraQuick Rapid HCV Test
http://money.cnn.com
Globe Newswire
BETHLEHEM, Pa., Jan. 7, 2010 (GLOBE NEWSWIRE) -- OraSure Technologies, Inc. (Nasdaq:OSUR) announced today the recent filing of a pre-market approval ("PMA") amendment with the U.S. Food and Drug Administration ("FDA") for the Company's OraQuick(R) Rapid HCV Antibody Test. The amendment contains additional clinical data requested by the FDA for use of the test in detecting antibodies to the Hepatitis C Virus ("HCV") in venous whole blood samples.
When approved for use with venous whole blood, the OraQuick(R) HCV test is expected to be the first rapid HCV test approved by the FDA for use in the United States. The Company is also currently completing an additional clinical study to obtain FDA approval of the OraQuick(R) HCV test for use with oral fluid and fingerstick whole blood.
Filing of the amendment with the FDA follows the Company's announcement this past December that it received approval to affix the CE mark to its OraQuick(R) HCV Test for use with oral fluid, fingerstick blood, venous whole blood, serum and plasma. The CE mark is required to sell this test in the 27 countries that currently make up the European Union. The OraQuick(R) Rapid HCV Antibody Test is the first and only rapid Hepatitis C test bearing a CE mark that can be used with oral fluid.
As previously announced, OraSure entered into agreements with Merck & Co., through its predecessor Schering Plough Corp., to collaborate on the development and promotion of the OraQuick(R) HCV test. Under these agreements, Merck will provide detailing and other promotional support for the test in the physicians' office markets in the United States and internationally.
About OraSure Technologies
OraSure Technologies develops, manufactures and markets oral fluid specimen collection devices using proprietary oral fluid technologies, diagnostic products including immunoassays and other in vitro diagnostic tests, and other medical devices. These products are sold in the United States as well as internationally to various clinical laboratories, hospitals, clinics, community-based organizations and other public health organizations, distributors, government agencies, physicians' offices, and commercial and industrial entities. For more information on the Company, please go to www.orasure.com.
The OraSure Technologies, Inc
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January 8, 2010
Hepatitis B Foundation Awards UT School of Public Health Professor
www.eurekalert.org
HOUSTON – (Jan. 8, 2010) – R. Palmer Beasley, M.D., Ashbel Smith Professor at The University of Texas School of Public Health, has been awarded the Hepatitis B Foundation's Distinguished Scientist Award 2010.
"The HBV vaccine, the first cancer vaccine, provides long-term protection against hepatitis B infection, which is responsible for a large proportion of liver cancer in the world. Ultimately, HBV can be eradicated," said Beasley. "This honor from the Hepatitis B Foundation provides another tool to encourage the world to use the vaccine vigorously."
For more than 18 years, Beasley served as dean of the UT School of Public Health. Beasley has pioneered work in perinatal hepatitis B virus transmission, which showed that mother-infant transmission was the most important factor in sustaining hepatitis B virus infection in Asia. He also did the definitive research that proved that hepatitis B causes primary liver cancer and led the global effort to convince the World Health Organization to establish the HBV vaccine as the first human cancer vaccine.
"Dr. Beasley's contributions to understanding the link between hepatitis B and liver cancer have saved thousands of lives. His work not only transformed our understanding of the cause of liver cancer, but then spearheaded the solution through vaccination," said Roberta B. Ness, M.D., dean of the UT School of Public Health. "We are certainly proud to call him one of our own."
This award is the highest scientific honor awarded by the foundation in recognition and appreciation for the research of hepatitis B.
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Prisoner Disease Levels Prompt Needle Exchange Calls
http://www.abc.net.au
High levels of hepatitis C in Canberra's new jail, the Alexander Maconochie Centre (AMC), has reignited the debate over a needle exchange program.
In June last year half the prisoners in the AMC volunteered to be tested and almost 60 per cent had the virus.
There were no recorded Hepatitis C transmissions and it is a small sample, but that is still higher than other jurisdictions.
Brian McConnell from Family and Friends for Drug Law Reform says the figure puts more pressure on the Government to introduce a needle exchange program.
"We know they're sharing syringes in prison," he said.
He says a needle exchange program would protect prisoners' health.
But Health Minister Katy Gallagher says it is a complex issue.
"We need staff to be able to feel safe in the workplace," she said.
Ms Gallagher says the Government will gather data for 18 months before making a decision.
"The difficulty with this argument is that if you choose an industrial side it's a very simple decision - don't have [a needle exchange program]," she said.
"If you choose a health side, it's a very simple decision - have one.
"I guess the job the Government's got to do is weigh up the evidence and look at how we reconcile those two competing issues."
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Researchers Find Genetic Explanation for Why Hepatitis C (HCV) Treatment Doesn't Work for Some
http://www.thebody.com
By Olivia Ford
Being infected with chronic hepatitis C (HCV) presents challenges no matter who you are. For instance, HCV has nowhere near the wealth of treatment options that we have for HIV. The HCV meds that are available can cause harsh side effects, and in many cases they don't work. Furthermore, there's a fact that has baffled HCV-positive people and their caregivers for years: It has long appeared that, if you're of African descent (as most black people are), as opposed to European descent (as most white people are), HCV treatment is considerably less likely to work for you.
Now, in a landmark study published in the journal Nature, U.S. researchers say they have discovered that people with a specific genetic variation appear to have better outcomes on standard HCV treatment. Here's the twist, however: About 39 percent of the whites in the study had the beneficial variation, compared with only about 16 percent of African Americans. As a result, the researchers believe that this variation (which occurs near the IL28B gene) may explain some of the differences between how African Americans and whites respond to HCV treatment.
(It's worth mentioning that African Americans who had the variation did significantly better on treatment than whites who did not have it – further evidence that it is the presence of this variation, and not race alone, that's associated with doing better on treatment.)
Of course, finding a major clue in a mystery as vexing as this one is cause for celebration. But what can people with HCV do with this information right now? We caught up with two of the researchers on this study – David Goldstein, Ph.D., and John McHutchinson, M.D., both of Duke University – and asked them everything we thought you'd want to know about this new research and what it means for the future of HCV treatment.
Olivia Ford: Had it been documented previously that African Americans did not do as well on HCV treatment as European Americans?
David Goldstein: This has been well known for a long time, and very well documented. It is one of the factors that persuaded us that there could well be a gene variant or variants that contribute to response.
Olivia Ford: Do you take into account the fact that many people of African descent are unaware that they have African ancestry and therefore don't self-identify as such?
David Goldstein: One of the most important points about this discovery is that the effect of IL28B status appears to be the same across different racial and ethnic groups. Hence it does not matter whether an individual is African American, Hispanic, European or [belongs to] presumably any other group. We still know that IL28B status will be informative about treatment response regardless of what group an individual is classified in.
Olivia Ford: Can someone be tested for the IL28B gene variation?
David Goldstein: I am hopeful that a test will be made available sooner rather than later so that both doctors and patients can incorporate that genetic information as treatment options are evaluated for individual patients.
Olivia Ford: Should everyone who's HCV positive be tested for this variation?
David Goldstein: In my opinion, most doctors and patients are likely to want to know IL28B status as they evaluate the best treatment options, and also factors such as treatment duration.
Olivia Ford: How soon do you think it will be before testing for the IL28B variation is recommended in the guidelines for HCV screening and care? In other words, when do you anticipate it becoming part of the basic workup for people with HCV?
John McHutchinson: Guidelines always lag behind the field, and they have just been revised for 2009 for HCV treatment. Nonetheless, updates and important changes can be made fairly quickly. I believe this will occur once a larger body of clinical evidence develops.
David Goldstein: I am hopeful this will happen within a very short period of time, hopefully only months. ... There does seem to be a very high level of interest in this, and I believe a test should indeed be made available.
Olivia Ford: Does this genetic variation equally affect treatment outcomes on every currently available treatment for HCV?
David Goldstein: So far, we have only studied pegylated interferon [Pegasys, Peginterferon, PEG-Intron] and ribavirin [Copegus, Rebetol] – the standard of care.
Olivia Ford: Is there alternative treatment for HCV that people can take if they turn out not to have the IL28B gene and existing treatments don't work for them?
David Goldstein: There are new treatments that are in late-stage evaluation. It will be a priority to determine how IL28B status influences response to these treatments.
John McHutchinson: In the future, direct antivirals (protease and polymerase inhibitors, for example) may be available. Some of these drugs are in phase 3 clinical trials globally now, and response rates appear higher. We have recently published on this in the New England Journal of Medicine. Telaprevir [VX-950] is the name of the newest drug coming through the pipeline.
Olivia Ford: What does the discovery of this IL28B variation mean for the development of future HCV treatments?
David Goldstein: One of the more interesting questions is whether one could develop add-on therapies that might help to make individuals with the "poor response" IL28B type respond more like individuals with the good response type.
Olivia Ford: Since no IL28B test is currently available, should a person who's African American – and therefore has a lesser likelihood of having this protective gene variation – delay starting treatment?
John McHutchinson: Not at all. But they can now be armed with additional information that will help them decide whether to undergo therapy now or defer therapy, depending on their degree of liver disease, IL28B type and other factors.
Olivia Ford: If someone is already on HCV treatment and is wondering about his or her IL28B status, should he or she consider stopping treatment?
John McHutchinson: No – we would never do that once we had committed to starting to treat someone, based on many other factors.
Olivia Ford: In light of the findings of your study, what can a person infected with HCV do today, right now, with this information – particularly if they're considering starting treatment?
David Goldstein: We definitely do not foresee that IL28B status would be used to either deny anyone therapy or to stop in mid-course. As far as African Americans go, I think one point to consider is that some African Americans may be reluctant to start therapy because they know, or are told, that as African Americans they have a relatively low chance of being cured.
But we can now do much better than that. We can determine their IL28B status and give them information that is specific to their individual genetic makeup, instead of the more crude proxy of their racial/ethnic grouping.
John McHutchinson: When such a test becomes available, providers will be armed with a pretty powerful additional piece of information to share with their patients, before therapy, about the likelihood of responding. No doubt this will help inform the decision-making process.
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