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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265772568233"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_217"
                     title="Herpes Therapy Doesn&apos;t Bar HIV Transmission (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18071?impressionId=1265772568233"
                     
      &lt;p&gt;Treating herpes has no effect on the transmission of HIV among discordant couples, researchers said.&lt;/p&gt;
&lt;p&gt;The lack of efficacy was found in a large, randomized clinical trial despite significant reductions in HIV viral load among those treated for herpes simplex-2 (HSV-2), according to Connie Celum, MD, of the University of Washington, and colleagues.&lt;/p&gt;
&lt;p&gt;Researchers will have to look for new ways to prevent transmission among discordant couples (in which one partner has HIV and the other does not), Celum and colleagues concluded online in the&lt;em&gt; New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The study comes after earlier trials also showed that treating HSV-2 with the antiviral acyclovir (Zovirax) did not lower the risk of getting HIV. (See &lt;a href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; mce_href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; target=&quot;_blank&quot;&gt;Herpes Treatment No Help in Preventing HIV&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The trials  --  and the current study  --  had their origins in epidemiological and laboratory observations that having an HSV-2 infection increased the risk of contracting HIV.&lt;/p&gt;
&lt;p&gt;Researchers reasoned that a converse effect might also be true  --  treating HSV-2 in HIV-negative people might reduce their risk of infection.&lt;/p&gt;
&lt;p&gt;The reasoning was bolstered by clinical trials showing that treating HSV-2 in HIV-positive people lowered their viral load.&lt;/p&gt;
&lt;p&gt;In the current study, that effect also occurred. HIV-positive volunteers treated with acyclovir saw, on average, a reduction in plasma concentration of HIV by 0.25 log&lt;sub&gt;10&lt;/sub&gt; copies per milliliter compared with members of the placebo group. The difference was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;But transmission among the couples was not affected, implying that a greater reduction in viral load is needed, the researchers said.&lt;/p&gt;
&lt;p&gt;The study, randomized and placebo-controlled, included 3,408 couples in Africa in which only one of the partners had HIV (but was not taking antiretroviral therapy) and also had an HSV-2 infection.&lt;/p&gt;
&lt;p&gt;The outcome was first reported at the Cape Town meeting of the International AIDS Society last year (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; target=&quot;_blank&quot;&gt;IAS: Acyclovir Flops in Preventing HIV Transmission&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The primary outcome was transmission between partners, verified by genetic sequencing of the virus.&lt;/p&gt;
&lt;p&gt;Transmission between partners was verified in 84 of the 132 recorded cases of transmission, the researchers said, and they were evenly divided  --  41 among those getting the drug and 43 in the placebo group.&lt;/p&gt;
&lt;p&gt;On the other hand, the use of the drug reduced the occurrence of herpes lesions by 73%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;The reduction of herpes lesions suggests that the drug was being used, the researchers said, and therefore that the lack of efficacy against HIV was not a result of nonadherence to acyclovir.&lt;/p&gt;
&lt;p&gt;Overall, the rate of HIV transmission in the study was 2.7 cases per 100 person-years, markedly lower than earlier observations. The researchers attributed that to such interventions as monthly counseling on risk reduction and free condoms.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study had support from the Bill and Melinda Gates Foundation, as well as the University of Washington, the National Institute of Allergy and Infectious Diseases, Gen-Probe, and the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Celum reported financial links with GlaxoSmithKline and several other authors reported links with various pharamceutical companies.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1318"
                     title="Antiviral Appears to Improve HCV Treatment"
                     score="-0.005"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/13981?impressionId=1265772568233"
                     
      TORONTO, April 29 -- Adding an antiviral drug to standard hepatitis C therapy shortened the treatment time and increased response rates, two studies found.
              &lt;p&gt; 
              &lt;p&gt;In the phase II studies, with slightly different designs, the investigational protease inhibitor telaprevir increased response rates by about 50%, the researchers reported in the April 30, 2009 issue of the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;The finding appears to be the first &quot;material advance&quot; in hepatitis C therapy since the introduction of pegylated interferon in 2001, according to Jay Hoofnagle, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.
              &lt;p&gt; 
              &lt;p&gt;Commenting on the studies in an accompanying editorial, Dr. Hoofnagle said the drug -- which inhibits a specific serine protease of the hepatitis C virus -- marks the &quot;beginning (of) a new era of treatment -- an era of antiviral agents developed specifically to target this virus.&quot;
              &lt;p&gt; 
              &lt;p&gt;In the first of the two studies -- both sponsored by the drug&apos;s developer --  John McHutchison, M.D., of Duke University, and colleagues randomized 250 patients with genotype 1 hepatitis C to one of four regimens.
              &lt;p&gt; 
              &lt;p&gt;The control group got standard therapy -- 48 weeks of ribavirin (Copegus, Rebetol) and peginterferon alfa-2a (Pegasys) -- and was compared with three other groups:
              &lt;p&gt; 
              &lt;ul&gt;
                &lt;li&gt;79 patients who got telaprevir for 12 weeks and 24 weeks of the standard drugs
                &lt;li&gt;79 patients who got 12 weeks of telaprevir and 48 weeks of standard therapy 
                &lt;li&gt;A small exploratory group of 17 patients who got telaprevir (1,250 milligrams on day one and 750 milligrams every eight hours thereafter) for 12 weeks, as well as peginterferon alfa-2a and ribavirin for the same 12 weeks
              &lt;/ul&gt;
              &lt;p&gt; 
              &lt;p&gt;The primary outcome was sustained virologic response, defined as an undetectable level of hepatitis C RNA 24 weeks after the end of therapy.
              &lt;p&gt; 
              &lt;p&gt;The researchers reported that the sustained virologic response rate was 41% in the control group, compared with 61% in the patients who got 12 weeks of telaprevir and 24 weeks of the standard drugs, a difference that was significant at &lt;em&gt;P&lt;/em&gt;=0.02.
              &lt;p&gt; 
              &lt;p&gt;The response rate was 67% in the patients who got 12 weeks of telaprevir and 48 weeks of the standard drugs, which was significant at &lt;em&gt;P&lt;/em&gt;=0.002, compared with standard therapy.
              &lt;p&gt; 
              &lt;p&gt;In the exploratory group, which was not compared with the control group, the rate was 35%.
              &lt;p&gt; 
              &lt;p&gt;Standard treatment &quot;cures less than half of patients and has significant side effects that make it very difficult for some patients to continue their treatment,&quot; Dr. McHutchison said in a statement. 
              &lt;p&gt; 
              &lt;p&gt;&quot;Our study found that by combining the standard therapy with the direct antiviral drug telaprevir, we could reduce the duration of treatment by 50%, to 24 weeks, and, at the same time, improve the cure rate by 50%.&quot;
              &lt;p&gt; 
              &lt;p&gt;One problem with telaprevir therapy was the incidence of adverse drug reactions -- primarily occurrence of rash -- which was higher than in the control group. This led to a higher rate of drug discontinuation than in the control group.
              &lt;p&gt; 
              &lt;p&gt;Results were similar in the second study, although the drug combinations analyzed were slightly different, according to Jean-Michel Pawlotsky, M.D., Ph.D., of the Henri Mondor Hospital in Paris, and colleagues.
              &lt;p&gt; 
              &lt;p&gt;The researchers compared outcomes in a control group of 82 patients who got standard therapy with outcomes among:
              &lt;p&gt; 
              &lt;ul&gt;
                &lt;li&gt;81 patients who got telaprevir for 12 weeks and 24 weeks of the standard drugs
                &lt;li&gt;82 patients who were treated with all three drugs for 12 weeks only
                &lt;li&gt;78 patients who got telaprevir and peginterferon alfa-2a -- without ribavirin -- for 12 weeks 
              &lt;/ul&gt;
              &lt;p&gt; 
              &lt;p&gt;The rate of sustained virologic response for the control group was 46%, compared with 69% in the patients who got telaprevir and 24 weeks of peginterferon alfa-2a ribavirin. The difference was significant at &lt;em&gt;P&lt;/em&gt;=0.004.
              &lt;p&gt; 
              &lt;p&gt;On the other hand, the rate in the other two telaprevir groups combined was not significantly different from that in the control group, the researchers found. 
              &lt;p&gt; 
              &lt;p&gt;They concluded that ribavirin was a critical part of the treatment regimen.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The studies were supported by Vertex Pharmaceuticals. 
              &lt;p&gt;Dr. McHutchison reported financial links with Vertex Pharmaceuticals, Schering-Plough, and Roche.
              &lt;p&gt;Dr. Pawlotsky reported financial links with Abbott, Astra-Zeneca, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Roche, Schering-Plough, Tibotec Pharmaceuticals, Valeant Pharmaceuticals, and Vertex Pharmaceuticals.
              &lt;p&gt;Dr. Hoofnagle reported no conflicts.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
         
    </recommendedItem>
    <recommendedItem id="20090101_19_2590"
                     title="Gene Variant Predicts HCV Treatment Success"
                     score="-0.005"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/15564?impressionId=1265772568233"
                     
      A small genetic change near the gene for interferon-lambda-3 doubles the chance of successful hepatitis C treatment, researchers said.&lt;br&gt;
&lt;br&gt;The variant  --  a cytosine for thymine switch on chromosome 19  --  is the first genetic marker that predicts response to treatment for genotype 1 hepatitis C, according to David Goldstein, PhD, of Duke University, and colleagues.&lt;br&gt;
&lt;br&gt;The alteration is also more common among people of European ancestry than those of African background, which may explain much of the difference in treatment response between the two ethnic groups, Goldstein and colleagues wrote online in &lt;em&gt;Nature&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;&quot;This is what personalized medicine is all about,&quot; Goldstein said in a statement. &quot;This discovery enables us to give patients valuable information that will help them and their doctors decide what is best for them.&quot;&lt;/p&gt;
&lt;p&gt;The finding comes from a genome-wide association study of more than 1,600 patients involved in the so-called IDEAL trial, which compared three treatment regimens for the disease. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/15192&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/15192&quot; target=&quot;_blank&quot;&gt;Head-to-Head Trial Finds HCV Regimens Equal&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Across all ethnic groups, the polymorphism was significantly associated (at &lt;em&gt;P&lt;/em&gt;=1.37x10&lt;sup&gt;-28&lt;/sup&gt;) with sustained virological response (SVR), defined as the absence of detectable virus at the end of follow-up.&lt;/p&gt;
&lt;p&gt;In patients of European ancestry who carry two copies of the C variant, the genotype was associated with a twofold greater rate of SVR than the TT genotype.&lt;/p&gt;
&lt;p&gt;The ratios were similar in both the African-American and the Hispanic populations in the study &amp;#8211; threefold and twofold, respectively, the researchers said.&lt;/p&gt;
&lt;p&gt;Interestingly, African-Americans with two copies of the C allele had a 53.3% SVR rate, significantly higher (at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) than the 33.3% seen in Europeans with two copies of the T allele.&lt;/p&gt;
&lt;p&gt;That finding, Goldstein and colleagues said, &quot;emphasizes the greater importance of individual genotype compared with ethnicity in predicting treatment response.&quot;&lt;/p&gt;
&lt;p&gt;In a random, multi-ethnic sample, whose hepatitis C status was not known, the C allele appeared in about 40% of African-Americans, compared with between 70% and 80% for European-Americans and Hispanics, Goldstein and colleagues said.&lt;/p&gt;
&lt;p&gt;East Asians, who are known to have even better SVR rates than Europeans, had the C allele more than 90% of the time, the researchers found.&lt;/p&gt;
&lt;p&gt;The researchers said they were struck by the finding that the CC genotype was beneficial to all subgroups, Goldstein said.&lt;/p&gt;
&lt;p&gt;&quot;But because it appears significantly more often among Caucasian populations than it does among African populations, we feel it explains much of the difference in response rates we see between African-Americans and those of European ancestry,&quot; he said.&lt;/p&gt;
&lt;p&gt;He and colleagues cautioned that the finding only applies to genotype 1 hepatitis C, which is the most common form. They said more research is needed to see if it applies to less common forms of the disease.  &lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the Schering-Plough Research Institute.&lt;/p&gt;&lt;p&gt;Goldstein reported financial links with Schering-Plough, and several authors are employees of the company.&lt;/p&gt;&lt;p&gt;Goldstein and other authors are inventors of a patent application based on this finding.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3475"
                     title="ASN: HCV Changes Dialysis Treatment Needs (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASN/tb/16712?impressionId=1265772568233"
                     
      &lt;p&gt;SAN DIEGO  --  Patients on dialysis need less epoetin to treat their anemia if they are infected with hepatitis C (HCV), a researcher reported here.&lt;/p&gt;
&lt;p&gt;HCV-positive patients also needed a lower dose of IV iron than their noninfected counterparts, even though they had similar hemoglobin levels, according to David Goodkin, MD, of the Arbor Research Collaborative for Health in Ann Arbor, Mich.&lt;/p&gt;
&lt;p&gt;This is a &quot;surprising, unusual finding,&quot; Goodkin said at the American Society of Nephrology meeting, because most inflammatory diseases, which interfere with the signal the bone marrow sends to make more red blood cells, would result in the need for a higher dose of epoetin.&lt;/p&gt;
&lt;p&gt;&quot;We speculate that it may be that this viral infection is actually stimulating the liver to make this hormone erythropoietin,&quot; Goodkin said, although he admitted that he doesn&apos;t know why the virus would activate the erythropoietin-producing cells.&lt;/p&gt;
&lt;p&gt;He said the finding would probably not affect clinical practice because patients on dialysis have their epoetin doses adjusted regularly anyway.&lt;/p&gt;
&lt;p&gt;&quot;The doctors are still going to follow the hemoglobin level and adjust the EPO dose,&quot; Goodkin said. &quot;This is just a clue that if it&apos;s hepatitis C-positive, they&apos;ll need less EPO, on average, than people who are hepatitis C-negative.&quot;&lt;/p&gt;
&lt;p&gt;Goodkin said he decided to investigate after he saw the results of a small case-control study from 2008, involving 66 patients, showing that those on dialysis who were infected with HCV needed significantly lower doses of erythropoietin (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01). There was also a trend toward lower IV iron requirements (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.07).&lt;/p&gt;
&lt;p&gt;To explore the issue on a larger scale, he turned to the prospective Dialysis Outcomes and Practice Patterns Study (DOPPS).&lt;/p&gt;
&lt;p&gt;The current analysis included 36,245 patients in 12 countries who were on hemodialysis, 7.8% of whom were positive for HCV.&lt;/p&gt;
&lt;p&gt;After adjusting for age, sex, race, years of hemodialysis, country, and 14 comorbidities, he and his colleagues found that the weekly epoetin dose was significantly lower in the HCV-positive patients (7,737 versus 8,210 Units, &lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;IV iron dose was also significantly lower in the infected patients (89.2 versus 96.4 mg/month, &lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Hemoglobin concentration was not significantly different in the two groups (&lt;em&gt;P&lt;/em&gt;=0.46).&lt;/p&gt;
&lt;p&gt;The odds ratios for not receiving epoetin or IV iron therapy among HCV-positive patients were 1.15 (&lt;em&gt;P&lt;/em&gt;=0.002) and 1.19 (&lt;em&gt;P&lt;/em&gt;=0.0002), respectively.&lt;/p&gt;
&lt;p&gt;Hepatitis B infection, on the other hand, offered no advantage.&lt;/p&gt;
&lt;p&gt;In addition to the unexpected effect of HCV infection on the epoetin dose, another surprising finding was that only seven infected patients in the study received antiviral treatment, including interferon.&lt;/p&gt;
&lt;p&gt;Goodkin speculated that clinicians might have been sparing the patients the adverse effects of antiviral therapy because most HCV-positive patients do not develop cirrhosis and liver failure, and patients on dialysis, many of whom are older, have a limited lifespan.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;DOPPS is funded by Amgen, Kyowa Hakko Kirin, and Genzyme.&lt;/p&gt;&lt;p&gt;Goodkin reported relationships with Affymax, AMAG Pharmaceuticals, Amgen, FibroGen, Keryx, Seattle Life Sciences, Xenon Pharmaceuticals, and Urodynamix Technologies.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>