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    <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=1265768717154"
                     
      &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_1748"
                     title="DDW: Telaprevir Improves HCV Clearance in Resistant Patients"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14515?impressionId=1265768717154"
                     
      CHICAGO, June 3 -- The investigational protease inhibitor telaprevir, added to standard hepatitis C (HCV) treatment, produced a sustained virologic response in about half of patients who had previously failed with conventional therapy, a phase IIb trial showed.
              &lt;p&gt; 
              &lt;p&gt;Patients who received telaprevir, peginterferon, and ribavirin had higher response rates than those who received peginterferon and ribavirin alone, the current standard treatment, according to Adrian Di Bisceglie, M.D., of Saint Louis University.
              &lt;p&gt; 
              &lt;p&gt;The group of patients who received telaprevir and peginterferon, but not ribavirin had less of a benefit than those who received all three drugs, he reported at Digestive Disease Week here.
              &lt;p&gt; 
              &lt;p&gt;Because there is no existing standard of care for patients who fail to respond to standard treatment for HCV, he said, &quot;I personally believe this . . . represents a new paradigm for how we will treat nonresponders in the future.&quot;
              &lt;p&gt; 
              &lt;p&gt;About three million people in the U.S. are infected with HCV, and about half will be able to clear the virus with peginterferon and ribavirin, according to Dr. Di Bisceglie.
              &lt;p&gt; 
              &lt;p&gt;Conducted at 53 centers, the PROVE3 (Protease Inhibition for Viral Evaluation) study follows the PROVE1 and PROVE2 studies, which evaluated the effect of telaprevir in treatment-naive patients. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/5444&quot; target=&quot;blank&quot;&gt;EASL: Telaprevir Shows Promise of Shortened Hepatitis C Therapy&lt;/a&gt; and &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AASLD/7285&quot; target=&quot;blank&quot;&gt;AASLD: Telaprevir Yields Good Response in Combo Therapy for HCV&lt;/a&gt;)
              &lt;p&gt; 
              &lt;p&gt;PROVE3 involved 453 patients with HCV genotype 1, the most common in the U.S. All had failed prior courses of treatment, either by having no virologic response, by relapsing after completing successful treatment, or by having the virus re-emerge before the end of treatment.
              &lt;p&gt; 
              &lt;p&gt;The patients were randomized to four treatment arms with varying duration of treatment with telaprevir, peginterferon, and ribavirin:
              &lt;p&gt; 
              &lt;ul&gt;
                &lt;li&gt;12 weeks of all three drugs followed by 12 weeks of standard treatment
                &lt;li&gt;24 weeks of all three drugs followed by 24 weeks of standard treatment
                &lt;li&gt;24 weeks of telaprevir and peginterferon, but no ribavirin
                 &lt;li&gt;24 weeks of placebo plus standard treatment followed by 24 weeks of standard treatment (control)
                            &lt;/ul&gt;
                              &lt;p&gt; 
                              &lt;p&gt;The median age of the patients was 51 and about two-thirds were male. All four groups were well-matched according to baseline characteristics.
                              &lt;p&gt; 
                              &lt;p&gt;The primary endpoint was sustained virologic response 24 weeks after the end of each treatment regimen.
                              &lt;p&gt; 
                              &lt;p&gt;All three telaprevir groups were superior to placebo in the percentage of patients who had a sustained virologic response at follow-up:
                              &lt;p&gt; 
                              &lt;ul&gt;
                                &lt;li&gt;51% in patients who received 12 weeks of telaprevir (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)
                                &lt;li&gt;52% in those who received telaprevir for 24 weeks along with standard treatment (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)
                                  &lt;li&gt;23% in those who did not receive ribavirin (&lt;em&gt;P&lt;/em&gt;=0.035)
                                    &lt;li&gt;14% in the controls
                                            &lt;/ul&gt;
                                              &lt;p&gt; 
                                              &lt;p&gt;Similar benefits were seen at four weeks, indicating a rapid virologic response, and immediately at the end of treatment.
                                              &lt;p&gt; 
                                              &lt;p&gt;Some patients relapsed between the end of treatment and the follow-up, 24 weeks later. The relapse rates were 30% and 13% in the two groups that received telaprevir plus standard treatment and 53% in both the group that did not receive ribavirin and the controls.
                                              &lt;p&gt; 
                                              &lt;p&gt;Notably, almost 40% of patients who had not responded to treatment at all before the study showed a sustained virologic response at follow-up in the two groups that received all three drugs (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both). That compared with only 9% of the controls.
                                              &lt;p&gt; 
                                              &lt;p&gt;Response rates of 69% and 76% were seen among prior relapsers (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both), with the higher rate occurring in those who received 48 weeks of standard treatment in addition to 24 weeks of telaprevir.
                                              &lt;p&gt; 
                                              &lt;p&gt;There was no difference in response rates between patients with and without cirrhosis.
                                              &lt;p&gt; 
                                              &lt;p&gt;&quot;It appears that telaprevir is able to overcome this and other traditional poor response factors,&quot; Dr. Di Bisceglie said.
                                              &lt;p&gt; 
                                              &lt;p&gt;The most common adverse events in groups receiving telaprevir were fatigue, nausea, headache, rash, itching, anemia, and gastrointestinal side effects, only some of which were severe enough to result in discontinuation.
                                              &lt;p&gt; 
                                              &lt;p&gt;The dosing regimen involving 24 weeks of all three drugs, followed by 24 weeks of peginterferon and ribavirin, is currently being evaluated in a phase III trial dubbed REALIZE.
                                              &lt;p&gt; 
                                              &lt;p&gt;Dr. Di Bisceglie said FDA approval for telaprevir is about two years away. Telaprevir and a similar drug, boceprevir, appear to be the closest to approval.
                                              &lt;p&gt; 
                                              &lt;p&gt;Patients with significant liver disease should receive treatment with peginterferon and ribavirin right away, he said, but patients who have previously failed a course of treatment might think about waiting for these drugs to hit the market.
                                              &lt;p&gt; 
                                              &lt;p&gt;&quot;These drugs are coming and not that far away, and it may be better to be waiting with our nonresponders for better treatment,&quot; he said.
                                              &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 supported by Tibotec and Vertex Pharmaceuticals, co-developers of telaprevir.
                                              &lt;p&gt; 
                                              &lt;p&gt;Dr. Di Bisceglie reported no conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
                                             
    </recommendedItem>
    <recommendedItem id="20090101_1_501"
                     title="AASLD: Peg-Interferon and Ifn-Ribavirin Combo Keep HCV in Check Long Term"
                     score="-0.005"
                     href="