<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265785715223"
                     
      &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="20090101_19_1258"
                     title="Sustained Response Seen with New Hepatitis C Drug"
                     score="-0.005"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/13894?impressionId=1265785715223"
                     
      WHEELING, W.Va., April 24 -- An investigational protease inhibitor for hepatitis C virus (HCV) infection showed promise in a phase II trial as add-on therapy, a researcher said.
              &lt;p&gt; 
              &lt;p&gt;Twice as many patients receiving boceprevir in addition to PEG-interferon-alfa2b (Pegintron) and ribavirin (Rebetol) achieved sustained virologic responses in a 48-week trial, compared with those receiving PEG-interferon and ribavirin alone (75% versus 38%, &lt;em&gt;P&lt;/em&gt;&lt;0.0001), reported Paul Kwo, M.D., of the Indiana University School of Medicine in Indianapolis.
              &lt;p&gt; 
              &lt;p&gt;The three-drug combination was most effective when boceprevir was added to the regimen four weeks after patients started on PEG-interferon and ribavirin.
              &lt;p&gt; 
              &lt;p&gt;Dr. Kwo presented updated results of the 595-patient randomized trial at the European Association for the Study of the Liver&apos;s annual meeting in Copenhagen.
              &lt;p&gt; 
              &lt;p&gt;He had reported preliminary results last November at a U.S. meeting. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AASLD/11620&quot; target=&quot;blank&quot;&gt;AASLD: Hepatologists Eye Protease Inhibitors for Hepatitis C&lt;/a&gt;)
              &lt;p&gt; 
              &lt;p&gt;Boceprevir is one of several investigational products in development that target the HCV NS3 protease enzyme.
              &lt;p&gt; 
              &lt;p&gt;The SPRINT-1 trial reported by Dr. Kwo tested six regimens containing boceprevir against PEG-interferon and ribavirin as the control in patients infected with HCV genotype 1.
              &lt;p&gt; 
              &lt;p&gt;PEG-interferon was given weekly at 1.5 mcg/kg.
              &lt;p&gt; 
              &lt;p&gt;Ribavirin doses ranged from 800 to 1,400 mg/day in all but one of the treatment arms; the study also included a low-dose ribavirin regimen in which doses ranged from 400 to 1,000 mg/day.
              &lt;p&gt; 
              &lt;p&gt;Boceprevir was given at 800 mg three times a day.
              &lt;p&gt; 
              &lt;p&gt;Treatment lasted 28 weeks in two of the boceprevir arms and 48 weeks in the other four.
              &lt;p&gt; 
              &lt;p&gt;Patients had high viral loads at baseline, above 600,000 IU/mL in 89%. Slightly more than half had genotype 1a HCV and 7% had evidence of cirrhosis.
              &lt;p&gt; 
              &lt;p&gt;The researchers found that &quot;rapid&quot; (undetectable HCV RNA within four weeks) and &quot;early&quot; (HCV undetectable within 12 weeks) virologic responses to treatment were highly predictive of responses maintained to the end the treatment.
              &lt;p&gt; 
              &lt;p&gt;From 74% to 100% of patients showing rapid responses also had sustained responses; 60% to 91% of those with rapid responses maintained them successfully.
              &lt;p&gt; 
              &lt;p&gt;Overall, the best results were seen with the 48-week regimen that included the four-week PEG-interferon and ribavirin lead-in.
              &lt;p&gt; 
              &lt;p&gt;Of 103 patients receiving this regimen, 77 achieved sustained virologic responses.
              &lt;p&gt; 
              &lt;p&gt;Other key results in this group included:
              &lt;p&gt; 
              &lt;ul&gt;
                &lt;li&gt;Relapse rate: 3%
                &lt;li&gt;Discontinuation rate from adverse events: 9%
                &lt;li&gt;Viral breakthrough rate: 5%
              &lt;/ul&gt;
              &lt;p&gt; 
              &lt;p&gt;In contrast, the relapse rate in the control group was 24% and the discontinuation rate was 8%.
              &lt;p&gt; 
              &lt;p&gt;Dr. Kwo also reported that the boceprevir regimen that included low-dose ribavirin was relatively ineffective. Sustained virologic responses were seen in only 36% of patients, with relapses in 23%, and viral breakthrough in 27%.
              &lt;p&gt; 
              &lt;p&gt;With the boceprevir regimen including full-dose ribavirin and no lead-in period, 67% of patients had sustained virologic responses, but 19% discontinued because of adverse events.
              &lt;p&gt; 
              &lt;p&gt;The two 28-week treatment regimens -- one with a four-week lead-in period before boceprevir was started, the other without -- led to sustained responses in 56% and 55% of patients, respectively, with relapse rates of 25% and 30%.
              &lt;p&gt; 
              &lt;p&gt;Fatigue, anemia, nausea, and headache were the most common adverse events reported in the boceprevir arms.
              &lt;p&gt; 
              &lt;p&gt;Treatment-emergent anemia was associated with sustained virologic responses, according to a press release issued by the study&apos;s sponsor, Schering-Plough.
              &lt;p&gt; 
              &lt;p&gt;The company said anemia occurred in about half of patients receiving boceprevir and more than one-third of the control group.
              &lt;p&gt; 
              &lt;p&gt;Erythropoietin was given to 26% of control patients and 39% to 51% of those in the boceprevir arms who also received standard-dose ribavirin.
              &lt;p&gt; 
              &lt;p&gt;Boceprevir is now being studied in two randomized phase III trials intended as registration studies, according to Schering-Plough.
              &lt;p&gt; 
              &lt;p&gt;Both include a lead-in with PEG-interferon and ribavirin before boceprevir is introduced.
              &lt;p&gt; 
              &lt;p&gt;The investigators believe the lead-in allows time to reach steady-state blood levels of the standard drug and for the interferon drug to prime the patient&apos;s immune system.
              &lt;p&gt; 
              &lt;p&gt;According to Schering-Plough, this approach may head off development of resistance to boceprevir.
              &lt;p&gt; 
              &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 study was funded by Schering-Plough.
              &lt;p&gt; 
              &lt;p&gt;Some of the study investigators were employees of Schering-Plough. No other potential conflicts of interest were reported.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
             
    </recommendedItem>
    <recommendedItem id="20090101_1_482"
                     title="AASLD: Weight-Based Dosing of Rebetol Improves Outlook for HCV"
                     score="-0.005"
                     href="