Friday, January 20, 2012

Hepatitis C Friday News Ticker: How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C?


    Today's Updates

    Clinical Trials

    This study will assess the safety and efficacy of alisporivir plus pegylated interferon alfa2a and Ribavirin as well as boceprevir plus pegylated interferon alfa2a and Ribavirin in African American chronic hepatitis C genotype 1 patients that have never received treatment for their hepatitis C.

    The purpose of this study is to evaluate the overall efficacy, and safety profile, of triple combination therapy of DEB025/pegIFN/RBV in chronic hepatitis C patients who failed prior treatment with PI.

    Clinical Trials 
    To learn more about Hepatitis C virus clinical trials or to find out if a study is enrolling patients in your area, please click here

    Source- NEJM Blog

    Treatment of Hepatitis C

    Posted by Sara Fazio • January 19th, 2012

    In a new study of 21 patients with hepatitis C virus genotype 1 infection who had had no response to prior treatment, sustained virologic responses were achieved in 4 of 11 who were treated with two antiviral agents alone and in 9 of 10 who were treated with the antiviral agents plus peginterferon and ribavirin.

    Approximately 180 million people worldwide are infected with hepatitis C virus (HCV), including 4.1 million in the United States. HCV infection is the most common cause of chronic liver disease in the United States and a leading cause of cirrhosis and hepatocellular carcinoma globally. HCV is classified into six major genotypes; genotype 1 is predominant in the United States and is the most difficult to treat.

    Clinical Pearls
    What is the conventional treatment and associated outcomes for Hepatitis C genotype 1 infection?

    Treatment of HCV genotype 1 infection with peginterferon alfa and ribavirin for 48 weeks results in sustained virologic response (undetectable HCV RNA 24 weeks after the end of therapy) in 40 to 50% of patients who have not received previous treatment. Patients are considered as not having had a response if they do not have a reduction in HCV RNA levels by at least 2 log10 IU per milliliter after a minimum of 12 weeks of treatment with peginterferon and ribavirin. Retreatment with triple therapy — a protease inhibitor, peginterferon, and ribavirin — yields rates of sustained virologic response of only 14 to 33%.

    In patients with HCV genotype 1 infection who have not had a response to prior therapy, what new regimens may be effective?

    In this week’s Journal, a preliminary study of patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents alone [the NS5A replication complex inhibitor BMS-790052 (60 mg once daily) and the NS3 protease inhibitor BMS-650032 (600 mg twice daily)]. In addition, a high rate of sustained virologic response at 24 weeks was achieved when the two direct-acting antiviral agents were combined with peginterferon and ribavirin.

    Table 2. Virologic Response during and after Treatment.

    Morning Report Questions
    Q: What medication-related adverse effects were most commonly reported in patients receiving treatment in this study?

    A: All the patients completed at least 24 weeks of therapy. The most common adverse events were diarrhea, fatigue, headache, and nausea, and were reported in both groups. Most adverse events were mild to moderate. There were no deaths, serious adverse events, or discontinuations due to adverse events during the analysis period.

    Q: What was the pattern of resistance seen in patients treated only with direct-acting antiviral agents?

    A: A high frequency of resistance to two classes of drugs was seen in patients with HCV genotype 1a infection who were treated with direct-acting antiviral agents alone. Although there were only two patients with HCV genotype 1b infection in this group, the observation that both of the patients had a sustained virologic response after treatment with two direct-acting antiviral agents alone may reflect a higher resistance barrier for this combination of drugs in patients with HCV genotype 1b infection than in patients  with HCV genotype 1a infection. In contrast to the former group, no viral breakthrough occurred in patients in the group receiving quadruple therapy

    Source- NEJM Blog
    Hope for Hepatitis C
    Posted by John Staples • January 18th, 2012


    Imagine, for a moment, that you recently received a brand new Time-O-Matic Time Machine as a gift. How far back would you have to set the dial to see that meaningful progress has been made in the treatment of hepatitis C?

    First, let’s say you set the dial to January 2011 and –- Puff-kachunk! — you’re there. Standard treatment for chronic hepatitis C genotype 1 infection consisted of 48 weeks of pegylated interferon-alpha and ribavirin, an approach more likely to produce adverse effects than clearance of the virus.

    Your next trip (Zing-kersplat!) takes you to May 2011. The oral serine protease inhibitors boceprevir and telaprevir have just become available for treatment of chronic HCV genotype 1 infection. When added to pegylated interferon and ribavirin, these direct-acting antivirals dramatically improve the rate of sustained virologic response (SVR). But many patients still do not respond to treatment, and medication intolerance remains an issue. You step into your Time-O-Matic and return to January 2012 feeling somewhat discouraged.

    Fortunately, this week’s NEJM might raise your spirits. In it, Dr. Anna S. Lok (University of Michigan, Ann Arbor, MI) and colleagues report on an open-label, phase 2a study that used a combination of two direct-acting antivirals to treat chronic HCV genotype 1 infection.

    Twenty-one ‘null responders’ (patients who failed to achieve ≥2log10 decline in HCV RNA after ≥12 weeks of peginterferon and ribavirin) were randomized to 24 weeks of treatment in one of two treatment arms:
    • Group A received BMS-790052 (an oral, first-in-class, NS5A replication complex inhibitor) and BMS-650032 (an oral NS3 protease inhibitor);

    • Group B received BMS-790052 and BMS-650032 plus peginterferon alfa-2a and ribavirin.
    Four of eleven (36%) patients in Group A and ten of ten (100%) of patients in Group B achieved an undetectable HCV RNA twelve weeks after completion of study treatment (SVR12, the primary end point). There were no deaths, serious adverse events, or discontinuations. The most common mild-to-moderate adverse effects were diarrhea, fatigue, headache, and nausea.

    These results are exciting. The high rate of SVR12 achieved in Group B suggests that more effective treatment regimens may soon be available for null responders. But for editorialist Dr Raymond T. Chung (Massachusetts General Hospital, Boston, MA), it’s the Group A proof-of-concept results that really put HCV therapy “on the threshold of a treatment revolution.” The 36% of Group A patients achieving SVR12 demonstrate that combination direct-acting antivirals with non-overlapping resistance profiles can achieve HCV clearance without the use of interferon. If interferon and its adverse effects can be avoided, there is hope that treatment might be offered and accepted by a much greater number of patients.

    “Current HCV treatment regimens are far from perfect,“ says primary care physician and NEJM deputy editor Dr. Mary Beth Hamel, “so it’s satisfying to see encouraging results from this kind of early-phase trial. It will be exciting to see what the future brings.”
    Curious? Go ahead. Step into the Time-O-Matic and set the dial to see how far HCV therapy has progressed by January 2017. The rest of us, however, will just have to wait.

    Medscape--
    FYI

    Spam mails apparently circulating across LinkedIn the business-related website for social networking inform recipients of somebody who has written to them, but actually conceal a sinister scheme for promoting a pharmaceutical website, which sells shady or illegitimate items, published softpedia.com dated January 12, 2012.

    The fake electronic mail tells the recipient that [Name] has written one message for him. By following the web-link embedded underneath the message, the recipient can read it. The web-link given asks to view or answer the message. Meanwhile, to avoid getting e-mail notifications the user requires adjusting its configurations, the e-mail concludes.

    But, when the web-link is clicked, the user is led onto one traditional pharmaceutical site that offers wonderful opportunities for buying medical items, a few illicit alternatively possible for acquiring solely through physician-prescribed certificates.

    Essentially pharmacy scams aren't infrequent; however, they appear as highly successful, else their perpetrators would've deserted them in favor of something more effective.
    A number of the fake Internet sites do not get displayed within search engine returns; therefore, cyber-crooks devise additional methods for advertising them. Hence the use of spam mails here as the more efficient tactic.

    Nevertheless, according to security experts, it's quite imprudent as also potentially harmful for purchasing drugs or medicines from any such fake pharmaceutical website.
    For, even suppose an ordered drug actually reaches the spam mail receiver, he has no way about verifying its authenticity as it could also be a harmful substitute. 

    Further, bogus pharmaceutical websites frequently have un-protected pages for manipulating transactions based on credit cards that can surely lead to theft of those cards' particulars. Besides, if anyone is suspected of intentionally using such spurious spam tricks, that person shouldn't be believed so far as giving him personal info or credit card particulars are concerned. Lastly, these fake online medicinal stores occasionally host malware too.

    Additionally, the spam mails in question utilize HTML for masking the true online sites their implanted web-links exhibit. However, by brushing the mouse over such web-links the underlying URLs will get exhibited, thus letting users to conveniently know whether or not the said web-links are camouflaged.
    SPAMfighter News - 20-01-2012

    For Your Reading Pleasure

    Grand Rounds
    Grand Rounds is a weekly summary of the best health blog posts on the Internet. Each week a different blogger takes turns hosting Grand Rounds, and summarizing the best submissions for the week.
    Hosted this week by Codeblog

    How’d we get to Volume 8 already?!  I think hosting this Grand Rounds finally ties me up with GruntDoc, who has hosted 7 times.  Grand Rounds is the weekly round-up of blog posts by medical bloggers.

    Whereas in the past the host would post nearly every link they received, it appears that we are now moving towards more curated content.  I said in my previous post that I wasn’t going to institute a theme, but I was definitely more drawn to the personal-story type posts.  Thanks to everyone that submitted!

     I shamelessly grabbed this next post from Twitter – Jordan, who blogs at In My Humble Opinion, wrote a touching post about mothers.  In Praise of Mothers wasn’t quite the post that I was expecting (and apparently the first commenter wasn’t expecting it either); it was even better.   And I’ve tried several times here to explain why, but I can’t.

    And I shamelessly grabbed this one from Google Reader – Dr. V at 33 Charts shares his answer to the question, “How Often Should A Physician Blog?“  You could easily take the word “physician” out and apply the answer to any blogger.  I have been blogging for over 9 years now.  My posting frequency in the very beginning was about once a week.   Now it’s more like once a month.  He has some great insights that I found myself completely agreeing with.
      Continue Reading Here.....

    Psychological research has found that religious people feel great about themselves, with a tendency toward higher social self-esteem and better psychological adjustment than non-believers. But a new study published in Psychological Science, a journal of the Association for Psychological Science, finds that this is only true in countries that put a high value on religion.

    The researchers got their data from eDarling, a European dating site that is affiliated with eHarmony. Like eHarmony, eDarling uses a long questionnaire to match clients with potential dates. It includes a question about how important your personal religious beliefs are and questions that get at social self-esteem and how psychologically well-adjusted people are. Jochen Gebauer of the Humboldt-Universit├Ąt zu Berlin, Constantine Sedikides of the University of Southampton, and Wiebke Neberich of Affinitas GmbH in Berlin, the company behind eDarling, used 187,957 people’s answers to do their analyses.

    As in other studies, the researchers found that more religious people had higher social self-esteem and where psychologically better adjusted. But they suspected that the reason for this was that religious people are better in living up to their societal values in religious societies, which in turn should lead to higher social self-esteem and better psychological adjustment. The people in the study lived in 11 different European countries, ranging from Sweden, the least religious country on the planet, to devoutly Catholic Poland. They used people’s answers to figure out how religious the different countries were and then compared the countries.

    On average, believers only got the psychological benefits of being religious if they lived in a country that values religiosity. In countries where most people aren’t religious, religious people didn’t have higher self-esteem. “We think you only pat yourself on the back for being religious if you live in a social system that values religiosity,” Gebauer says. So a very religious person might have high social self esteem in religious Poland, but not in non-religious Sweden.

    In this study, the researchers made comparisons between different countries, but another study found a similar effect within one country, between students at religious and non-religious universities. “The same might be true when you compare different states in the U.S. or different cities,” Gebauer says. “Probably you could mimic the same result in Germany, if you compare Bavaria where many people are religious and Berlin where very few people are religious.”

    ###
    For more information about this study, please contact: Jochen E. Gebauer at mail@JochenGebauer.info.

    The APS journal Psychological Science is the highest ranked empirical journal in psychology. For a copy of the article "Religiosity, Social Self-Esteem, and Psychological Adjustment: On the Cross- Cultural Specificity of the Psychological Benefits of Religiosity" and access to other Psychological Science research findings, please contact Divya Menon at 202-293-9300 or dmenon@psychologicalscience.org.

     
    For Your Viewing Pleasure



    Several recent large-scale research reviews have provided the best evidence yet that chocolate, derived from the seeds of the cocoa tree (Theobroma cacao), is good for your heart. 

    In one review, in the British journal BMJ in August, researchers analyzed data from seven observational studies, which included more than 100,000 people. Those who ate the most chocolate had a 37 percent lower risk of heart disease, compared to those eating the least, after controlling for weight, physical activity, education and other dietary factors that could influence the results. They were also 29 percent less likely to have a stroke. 

    In a second review, in the European Journal of Clinical Nutrition in August, Harvard researchers looked at 10 clinical studies from the last decade, with a total of 320 people. Consuming dark chocolate or cocoa products for 2 to 12 weeks modestly lowered cholesterol. And another review of clinical trials, in BMC Medicine, found that cocoa-rich products had a small blood-pressure-lowering effect in people with hypertension and prehypertension.
    Behind the benefits

    Chocolate’s health benefits are largely attributed to polyphenol compounds called flavonoids—the same family of substances that are in tea, red wine, grape juice and other plant foods—which have antioxidant, anti-inflammatory and anti-clotting properties. In particular, flavonoids increase production of nitric oxide, which helps relax and dilate blood vessels, and this may help lower blood pressure and have other cardiovascular effects. Cocoa flavonoids may also inhibit cholesterol absorption as well as oxidation of LDL (“bad”) cholesterol, making it less harmful.
    But before you reach for a chocolate bar, there are some caveats. First, not all studies have had positive results. And many—including all of those in the recent BMJ analysis—are observational studies, meaning that they don’t prove cause and effect (that chocolate, rather than something else about chocolate eaters, is responsible for the benefits seen). 

    Moreover, no one knows what type or amount of chocolate is optimal. Studies have used different formulations (with widely varying flavonoid levels) and intakes (from tiny daily amounts to impractically large quantities); some have not distinguished between milk and dark chocolate. Chocolate may affect people differently, too, depending on a variety of factors. 

    Keep in mind also that the chocolate confections that Americans love most are loaded with sugar, fat and calories (235 in a typical 1.5-ounce bar). Many have caramel, nougat and other unhealthy fillings and ingredients. Eat too much of any kind of chocolate and you can gain weight, which would likely cancel out the heart benefits.
    Chocolate morsels
    Not all chocolate is created equal. Processing of cocoa beans into commercial chocolate candy greatly reduces flavonoid levels. In fact, a main manufacturing objective is to remove these compounds because they have a bitter taste. Some companies use—or claim to use—methods that better preserve the heart-healthy compounds.
    Dark chocolate generally has more flavonoids than milk chocolate, but it’s hard to know how much a particular bar has. The percent cocoa (or cacao) listed on a label is not a reliable indicator of flavonoid content, and a bar that is, say, 70 percent cocoa from one manufacturer is not necessarily better than one that is 60 percent from another manufacturer. In addition to processing, the type of cocoa beans used and the manufacturer’s “recipe” also play a significant role in determining final flavonoid content. At the very least, the darker the chocolate, as indicated by a higher percent of cocoa solids, the less room there is for sugar.

    Though chocolate is high in saturated fat (from cocoa butter), this is mostly stearic acid, which has a neutral effect on blood cholesterol. On the other hand, milk chocolate has added fats that are not good for your heart, as well as more added sugar than dark chocolate. Milk chocolate has twice as much sugar as the darkest chocolate.
    Cocoa powder is highest in cocoa solids and has the most flavonoids—though “Dutch” (or alkali) processing destroys them. If you use cocoa powder, look for unsweetened natural versions. Next highest in flavonoids is unsweetened baking chocolate.
    Chocolate contains small amounts of caffeine—about 20 milligrams in an ounce of dark chocolate, and 6 milligrams in milk chocolate (compared to about 100 to 150 milligrams in a cup of coffee).

    It’s not clear whether adding milk to cocoa interferes with the absorption of flavonoids. A 2009 study in the American Journal of Clinical Nutrition, for instance, found reduced flavonoid absorption when people drank cocoa made with milk compared to cocoa made with water. Still, other studies have found no effect of milk on cocoa flavonoids and no difference in blood antioxidant levels. It’s possible that milk interferes with some, but not all, cocoa flavonoids. Some studies that found no milk interactions used cocoa with much higher flavonoid levels than those in commercial cocoa, which could make any flavonoid-reducing effect of the milk less apparent.

    Chocoholic advice
    Chocolate may provide some heart-health benefits, especially if you eat it in place of other snacks or desserts that are high in calories and saturated fat. Choose the darkest chocolate that you like. Cocoa beans or some variation, such as cacao, chocolate liquor or cocoa mass, should be the first ingredient, not sugar. But even if it’s rich in flavonoids, think of chocolate as a treat, not a health food, because of its hefty calories. Fruits and vegetables are a better source of flavonoids on a daily basis—they have fewer calories and an abundance of vitamins and minerals, along with other healthy plant compounds and fiber. 

    UC Berkeley Wellness Letter, February 2012
     
    In Case You Missed It

    BMS-650032 (Asunaprevir)
    BMS-790052 (Daclatasvir)

    By Gene Emery
    NEW YORK (Reuters Health) Jan 18 - Combining the experimental oral drugs asunaprevir and daclatasvir with the established treatment of peginterferon alfa-2a and ribavirin eliminated all traces of hepatitis C virus (HCV) in the blood of every volunteer, even after ribavirin-peginterferon alfa-2a treatment had already failed, in small phase II study released online today by the New England 

    Journal of Medicine.
    The ten patients treated with all four drugs all had undetectable viral levels 12 weeks after treatment stopped, and nine still had undetectable levels after 24 and 48 weeks.
    Another 11 patients received only asunaprevir and daclatasvir, and four of them had a sustained virologic response at 12 and 24 weeks after treatment.

    "This is a watershed moment in the annals of HCV therapy because it shows that a sustained virologic response can be achieved without interferon," Dr. Raymond T. Chung of Massachusetts General Hospital wrote in an editorial in the January 19 issue.
    Dr. Anna Lok of the University of Michigan and chief author of the study told Reuters Health that the cure rate for the peginterferon/ribavirin regime is low. "It's only 36%. But considering that these are difficult patients to treat, 36% is not too bad," she said.

    All 21 patients in the current study had genotype 1 HCV, the most common in the U.S., and all had failed to respond to peginterferon plus ribavirin (i.e., they had not had at least a 2 log10 decline in HCV RNA after at least 12 weeks of treatment).

    The response was far better when the four drugs were used. By the end of treatment, at week 24, all 10 patients in that group had undetectable levels of HVC RNA. Forty-eight weeks after the end of therapy, only one had any trace of the virus, and the amount was too small to quantify, according to the researchers.
    About 4.1 million people in the United States and 180 million worldwide are infected by hepatitis C, with its associated risk of cirrhosis and liver cancer.

    In the randomized phase II study, where patients knew what treatment they were getting, everyone received 600 mg of asunaprevir twice daily and 60 mg of daclatasvir once daily for 24 weeks. Both are made by Bristol-Myers Squibb, which paid for the trial.
    Ten of the 21 also got 180 mcg of Pegasys brand peginterferon alfa-2a each week and Copegus brand ribavirin, where the daily dose was 1,000 mg for those weighing less than 75kg and 1,200 mg for those weighing more. Both are Roche products.

    After 24 weeks of therapy, all 10 patients getting the four-drug regimen and five of the 11 patients receiving the non-interferon regimen had no trace of virus in their blood.
    The six patients in the non-interferon group who had viral breakthrough during the treatment period all had HCV genotype 1a. Another patient in that group had viral recurrence after treatment ended.
    By 24 weeks after treatment ended, the virus had returned in one of the 10 getting all four drugs. But that one person was retested 13 days after recurrence and levels of HCV RNA were undetectable, a phenomenon that was seen in other patients, said Dr. Lok. "Because it was not persistent, we believe 100% actually maintained virus clearance all the way to week 48."

    "To be able to get to 90% or 100% is very remarkable," she said. "On the other hand, we all know that a lot of patients can't handle interferon and ribavirin because of the side effects. What we hear from the patients is that they hate interferon. They prefer not to get treatment. Everyone is looking for when can we have an interferon-free regimen."

    In the new study, the side effects were similar in the two experimental groups. The three most common were diarrhea, fatigue and headache, reported by 45% to 73% of patients. Six patients had transient elevations of alanine aminotransferase to more than 3 times the upper limit of normal. Side effect rates were complicated by the fact six of the 11 volunteers randomized to receive only daclatasvir and asunaprevir received rescue therapy with interferon and ribavirin after a viral breakthrough.

    None of the 21 dropped out because of the side effects.
    Dr. Lok said 48 weeks of peginterferon and ribavirin usually costs about $40,000. Adding a protease inhibitor as a third drug costs another $50,000, and new biologicals often go for a comparable amount.

    The eventual price of the experimental drugs is not known, assuming they are approved.
    Thus, a four-drug regimen would add to the cost, Dr. Lok said, but "if this pans out, it's only 24 weeks of treatment. And if you get a cure once and for all, you don't have to worry about managing the complications of cirrhosis, liver transplant, liver cancer down the road."
    N Engl J Med 2012; 366:216-224.

    This study is not yet open for participant recruitment.
    Verified on January 2012 by Bristol-Myers Squibb

    First Received on December 2, 2011.   Last Updated on January 3, 2012   History of Changes


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