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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"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265774984494"
                     
      &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_226"
                     title="ASCO GI: Blood Test Detects Colorectal Cancer"
                     score="-0.004"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18079?impressionId=1265774984494"
                     
      &lt;p&gt;ORLANDO  --  A novel blood test that measures CD24 protein levels may detect early colorectal cancer and precancerous adenomas, researchers found.&lt;/p&gt;
&lt;p&gt;The investigational assay had 78.4%% sensitivity and 86.8% specificity for distinguishing patients with colorectal adenoma or cancer from healthy controls in a study led by Sarah Kraus, PhD, of Tel Aviv Souraski Medical Center in Israel.&lt;/p&gt;
&lt;p&gt;Further validation for the biomarker would be needed before considering clinical use in surveillance, they cautioned here at the ASCO Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;But the results were exciting and could represent &quot;a very significant advance,&quot; commented Robert P. Sticca, MD, of the University of North Dakota in Grand Forks.&lt;/p&gt;
&lt;p&gt;&quot;It looks like it may be a very reliable marker for not only the early detection of colon cancer and even precancerous conditions, but also could be used for follow-up for patients who previously had cancer for recurrence,&quot; he said as moderator of a press briefing at which the results were discussed.&lt;/p&gt;
&lt;p&gt;Colorectal cancer screening is effective, with early detection and treatment shown to improve survival.&lt;/p&gt;
&lt;p&gt;However, colorectal cancer is often diagnosed at a late stage with poor prognosis, in part because of &lt;a href=&quot;http://www.medpagetoday.com/Gastroenterology/ColonCancer/10115&quot; mce_href=&quot;http://www.medpagetoday.com/Gastroenterology/ColonCancer/10115&quot; target=&quot;_blank&quot;&gt;poor uptake of colonoscopy&lt;/a&gt;, Kraus said at the press briefing.&lt;/p&gt;
&lt;p&gt;Unfortunately, there are no sufficiently accurate blood-based screening tests, he noted, although there have been &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ECCO-ESMO/16057&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ECCO-ESMO/16057&quot; target=&quot;_blank&quot;&gt;attempts&lt;/a&gt; to develop them.&lt;/p&gt;
&lt;p&gt;Her group had previously found that the CD24 protein  --  expressed on the cell surface, where it plays a role in cell adhesion and metastasis  --  was associated with development of colorectal cancer in a gene expression study.&lt;/p&gt;
&lt;p&gt;So, with two independent cohorts, they tested whether CD24 could be a good biomarker for colorectal cancer.&lt;/p&gt;
&lt;p&gt;The first cohort included 63 patients with colorectal cancer, 19 with adenoma, and 68 controls with a clean bill of health on colonoscopy. Of these 150 individuals, 143 were externally evaluated by a blinded investigator.&lt;/p&gt;
&lt;p&gt;CD24 expression was nearly six-fold higher among adenoma and colorectal cancer cases than among controls, a significant difference. Levels were similar between the cancer and adenoma groups.&lt;/p&gt;
&lt;p&gt;The second cohort included 73 subjects: 38 normal controls, 24 with colorectal adenoma, and 11 with colorectal cancer.&lt;/p&gt;
&lt;p&gt;The test could distinguish colorectal cancer cases from controls with &quot;relatively high&quot; sensitivity and specificity (92.3% and 83.8%, respectively), Kraus said.&lt;/p&gt;
&lt;p&gt;Its performance in detecting adenoma versus normal colonoscopy results was lower, 75.0% sensitivity and 89.2% specificity.&lt;/p&gt;
&lt;p&gt;Kraus said her group is now testing this CD24 approach in a larger sample and developing an enzyme-linked immunosorbent assay (ELISA) that could be more widely used.&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 researchers reported no conflicts of interest.&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=1265774984494"
                     
      &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>
    <recommendedItem id="20090101_19_1748"
                     title="DDW: Telaprevir Improves HCV Clearance in Resistant Patients"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14515?impressionId=1265774984494"
                     
      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_5_298"
                     title="NKF: HCV Outbreaks at Dialysis Units Linked to Outmoded Infection Control"
                     score="-0.007"
                     href="