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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="0.002"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265778143111"
                     
      &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_1759"
                     title="DDW: Interferon Has Long-Term Histo Benefits in HCV"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14532?impressionId=1265778143111"
                     
       CHICAGO, June 3 -- A single course of interferon-based therapy, with or without ribavirin, produces long-term improvements in liver histology in patients with hepatitis C (HCV) who completely clear the virus, researchers found.
              &lt;p&gt; 
              &lt;p&gt;Patients who had a sustained virologic response had significant reductions in inflammation and fibrosis of the liver five or six years after receiving treatment, Mitchell Shiffman, M.D., of Virginia Commonwealth University, reported at Digestive Disease Week here.
              &lt;p&gt; 
              &lt;p&gt;Even half of the patients who had cirrhosis improved if they responded to therapy.
              &lt;p&gt; 
              &lt;p&gt;&quot;We used to think that once you had cirrhosis, it was sort of a done deal, and no matter what happened, you couldn&apos;t get any improvement,&quot; said co-investigator Richard Sterling, M.D., also at Virginia Commonwealth. &quot;But this study now confirms that some of those patients can actually resolve their liver scarring and inflammation.&quot;
              &lt;p&gt; 
              &lt;p&gt;Conversely, patients who declined or did not respond to treatment had significantly more inflammation and worsened fibrosis on a follow-up biopsy.
              &lt;p&gt; 
              &lt;p&gt;Several studies have shown that patients with chronic HCV can develop increased liver fibrosis over time. But the long-term impact of interferon-based therapy (in patients with and without a sustained virologic response) remained unknown, Dr. Sterling said.
              &lt;p&gt; 
              &lt;p&gt;Uncontrolled studies have shown that patients with a sustained virologic response have improvements in liver histology following a single course of interferon-based therapy, he said.
              &lt;p&gt; 
              &lt;p&gt;There has even been some suggestion that patients who do not have a response to therapy have reduced scarring in the short term, he said.
              &lt;p&gt; 
              &lt;p&gt;To explore the issue, Drs. Shiffman and Sterling and their colleagues began a prospective, longitudinal cohort study in 1991.
              &lt;p&gt; 
              &lt;p&gt;They included all patients who had a liver biopsy and either declined treatment (46 patients) or received a single course of interferon-based therapy, with or without ribavirin (287 patients).
              &lt;p&gt; 
              &lt;p&gt;All patients received a follow-up biopsy five or six years later. Most studies looking at the effect of therapy on liver histology have only followed up at 24 or 48 weeks, Dr. Sterling said.
              &lt;p&gt; 
              &lt;p&gt;The patients who decided not to undergo treatment generally had mild disease, as indicated by lower inflammation and fibrosis scores and lower serum alanine aminotransferase.
              &lt;p&gt; 
              &lt;p&gt;Of those who underwent treatment, 185 did not have a sustained virologic response and 102 did.
              &lt;p&gt; 
              &lt;p&gt;Patients who declined treatment and those who underwent treatment but failed to respond had similar increases in both inflammation and fibrosis of the liver (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for all comparisons). There were no differences between the two groups at follow-up.
              &lt;p&gt; 
              &lt;p&gt;Factors that predicted fibrosis progression were the changes in total inflammation and interface hepatitis from baseline (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.005 for both), and the degree of interface hepatitis at baseline (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).
              &lt;p&gt; 
              &lt;p&gt;The findings remained the same regardless of the degree of scarring at baseline.
              &lt;p&gt; 
              &lt;p&gt;In patients who had a sustained virologic response, inflammation and fibrosis of the liver both improved over time.
              &lt;p&gt; 
              &lt;p&gt;Of patients who had early scarring, or portal fibrosis, at baseline and had a sustained virologic response, 73% lacked any fibrosis at follow-up while 20% remained unchanged.
              &lt;p&gt; 
              &lt;p&gt;Of patients who had bridging fibrosis on the first biopsy and had a sustained virologic response, 35% were free from fibrosis at follow-up. Some 23% had reduced fibrosis, while 38% remained unchanged, and 4% progressed to cirrhosis.
              &lt;p&gt; 
              &lt;p&gt;And of patients who started out with cirrhosis and had a sustained virologic response, half improved: 10% had no fibrosis at follow-up. while 10% had improved to portal fibrosis, and 30% had improved to bridging fibrosis.
              &lt;p&gt; 
              &lt;p&gt;&quot;The results of our study show that in patients who respond to treatment, the use of interferon or peginterferon in addition to ribavirin is very effective,&quot; Dr. Sterling 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; Dr. Shiffman reported receiving research grants from Gilead Sciences, GlaxoSmithKline, Human Genome Sciences, Roche, Schering-Plough, Vertex Pharmaceuticals, Biolex, Valeant, Pfizer, Idenix, and Wyeth Pharmaceuticals, consulting or advising for Roche, Andys, Schering-Plough, Vertex, and Pfizer, and serving as a speaker for Roche and Schering-Plough.
              &lt;p&gt; 
              &lt;p&gt;Dr. Sterling reported no conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_3460"
                     title="ACG: HCV Drives Down Kidney Function (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ACG/tb/16690?impressionId=1265778143111"
                     
      &lt;p&gt;SAN DIEGO  --  Hepatitis C infection almost doubles the risk of chronic kidney disease and significantly increases progression to end-stage renal disease, according to data reported here.&lt;/p&gt;
&lt;p&gt;The association remained significant regardless of whether chronic kidney disease was defined in terms of creatinine clearance, proteinuria, glomerular filtration rate (GFR), or a combination of the parameters, according to Sanjaya Satapathy, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.&lt;/p&gt;
&lt;p&gt;The disparity between patients who have HCV infection and those who don&apos;t increased with age, reaching a five-fold difference in the prevalence of chronic kidney disease in patients older than 70, Satapathy said in a presentation at the American College of Gastroenterology meeting.&lt;/p&gt;
&lt;p&gt;&quot;There is a higher prevalence of chronic kidney disease and proteinuria in patients with hepatitis C infection,&quot; he said. &quot;Baseline viral load is higher in patients with chronic kidney disease and is an independent positive predictor for chronic kidney disease.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Progression to chronic kidney disease and end-stage renal disease is more rapid in patients with HCV infection,&quot; he added. &quot;Progression to chronic kidney disease is independent of diabetes.&quot;&lt;/p&gt;
&lt;p&gt;&quot;We conclude that hepatitis C is associated with the development of chronic kidney disease and poorer renal survival.&quot;&lt;/p&gt;
&lt;p&gt;Several lines of evidence have linked HCV infection and kidney disease. HCV has been reported to cause glomerular disease, increase the risk of albuminuria, and accelerate progression of diabetic nephropathy. Additionally, HCV particles or antigens have been identified in glomeruli and tubules, said Satapathy. However, data on the association have been inconsistent.&lt;/p&gt;
&lt;p&gt;Satapathy and his colleagues hypothesized that HCV increases the risk of chronic kidney disease and accelerates its progression.&lt;/p&gt;
&lt;p&gt;To test the hypothesis they performed a retrospective analysis of medical records on HCV-positive patients seen between January 2003 and October 2006 in a gastroenterology clinic. Patient data were traced back to June 1, 1999 or the date of first visit.&lt;/p&gt;
&lt;p&gt;The chart review yielded 552 patients who tested positive for anti-HCV antibodies. They were matched with a 313-patient, non-HCV, control group.&lt;/p&gt;
&lt;p&gt;Satapathy and colleagues used two sets of criteria to define chronic kidney disease.&lt;/p&gt;
&lt;p&gt;One definition stipulated persistence of proteinuria and/or serum creatinine &amp;gt;1.5 mg/dL in men or &amp;gt;1.3 mg/dL in women for more than three months.&lt;/p&gt;
&lt;p&gt;The second definition conformed to the National Kidney Foundation (NKF) guidelines that include structural or functional evidence of kidney damage for three months or GFR &amp;lt;60mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; for three months with or without evidence of kidney damage.&lt;/p&gt;
&lt;p&gt;Proteinuria was defined as &amp;#8805;30 mg/dL by dipstick measurement, and investigators used three months as the cutoff between intermittent and persistent proteinuria.&lt;/p&gt;
&lt;p&gt;The HCV and control groups did not differ with respect to baseline characteristics, with the exception of a higher prevalence of HIV infection (7.6% versus 1.3%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0005) and positive history of injection drug use (23.2% versus 1.9%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0005) in the HCV group.&lt;/p&gt;
&lt;p&gt;At baseline, 3.3% of the HCV group and 3.2% of the control group had chronic kidney disease, as defined by NKF criteria.&lt;/p&gt;
&lt;p&gt;At follow-up, the prevalence had increased to 8.3% in the HCV-positive group compared with 4.5% of the control group (&lt;em&gt;P&lt;/em&gt;=0.032).&lt;/p&gt;
&lt;p&gt;Combining proteinuria with GFR resulted in a prevalence of 9.6% in the HCV group and 5.1% in the control group (&lt;em&gt;P&lt;/em&gt;=0.019).&lt;/p&gt;
&lt;p&gt;When chronic kidney disease was defined by serum creatinine level, 6.7% of the HCV group and 3.5% of the control group had chronic kidney disease (&lt;em&gt;P&lt;/em&gt;=0.049).&lt;/p&gt;
&lt;p&gt;Adding proteinuria to serum creatinine resulted in rates of 7.8% and 4.2% in the HCV and control groups, respectively (&lt;em&gt;P&lt;/em&gt;=0.037).&lt;/p&gt;
&lt;p&gt;Analysis of the data by age groups, showed that 1% to 2% of patients younger than 40 had chronic kidney disease in both the control and HCV groups.&lt;/p&gt;
&lt;p&gt;With increasing age, more patients in the HCV group had chronic kidney disease compared with the control group, although none of the differences was statistically significant: &lt;ul&gt; &lt;li&gt;40 to 49, 4.6% versus 3%&lt;/li&gt; &lt;li&gt;50 to 59, 9.8% versus 5.2%&lt;/li&gt; &lt;li&gt;60 to 69, 22.7% versus 10.9% (&lt;em&gt;P&lt;/em&gt;=0.083)&lt;/li&gt; &lt;li&gt;&amp;gt;70, 40% versus 8.3% (&lt;em&gt;P&lt;/em&gt;=0.054)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Rates of intermittent proteinuria were similar between the groups, but HCV patients had a significantly greater rate of persistent proteinuria (6.8% versus 2.9%, &lt;em&gt;P&lt;/em&gt;=0.024).&lt;/p&gt;
&lt;p&gt;HCV had a significant adverse effect on kidney survival compared with the control group, whether defined by onset of chronic kidney disease (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0005) or time to end-stage renal disease (&lt;em&gt;P&lt;/em&gt;=0.005). HCV infection had a similar adverse effect on renal survival in patients with and without diabetes.&lt;/p&gt;
&lt;p&gt;Satapathy reported that HCV patients who developed CKD had significantly higher baseline viral loads (&lt;em&gt;P&lt;/em&gt;=0.006).&lt;/p&gt;
&lt;p&gt;A similar relationship was observed in a second, smaller study reported at the meeting. That study involved 19 HCV-positive patients who had a persistently elevated viral load (&amp;gt;1 million copies/mL) during follow-up for more than 1.5 years and 17 HCV patients who had a persistently low viral load (&amp;lt;10,000 copies/mL) during follow-up.&lt;/p&gt;
&lt;p&gt;At the beginning of follow-up, patients in the two groups had similar kidney function (GFR 110 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; in patients with a high viral load and 96 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; in the patients with a low viral load), said Fadi Rzouq, MD, of the University of Washington in Seattle.&lt;/p&gt;
&lt;p&gt;During 2.6 years of follow-up during which time none of the patients received treatment for HCV, mean GFR decreased by 27.6 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; in patients with a persistently elevated viral load, whereas GFR declined by &amp;lt;0.2 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; during 1.9 years of follow-up in the patients who had a persistently low viral load (&lt;em&gt;P&lt;/em&gt;=0.003).&lt;/p&gt;
&lt;p&gt;The results &quot;point toward the possibility of a direct renal toxicity induced by HCV, although this conclusion needs to be confirmed by more studies,&quot; said Rzouq.&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;Satapathy and co-investigators reported no disclosures.&lt;/p&gt;&lt;p&gt;Rzouq reported no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_9_391"
                     title="DDW: Relapsed HCV Patients Achieve Sustained Response with 72-Week Treatment"
                     score="-0.005"
                     href="