<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_344"
                     title="FDA Revises HIV Drug Label for Liver Complication"
                     score="0.009"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18229?impressionId=1265764519771"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has updated labels of the HIV drug didanosine (Videx and Videx EC) to include warnings for potentially serious liver damage.&lt;/p&gt;
&lt;p&gt;Although these cases are rare, the drug may cause noncirrhotic hypertension in patients, a potentially fatal complication which the FDA discovered through 42 postmarket, adverse event reports.&lt;/p&gt;
&lt;p&gt;Of those patients, three required liver transplant and four died. Two deaths were caused by esophageal hemorrhage, while two more were caused by progressive liver failure.&lt;/p&gt;
&lt;p&gt;One patient suffered multiorgan failure, cerebral hemorrhage, sepsis, and lactic acidosis.&lt;/p&gt;
&lt;p&gt;The FDA said in a statement that it chose not to recall the drug because it believes its benefits outweigh potential risks, but advised that treatment decisions be made on an individual basis between healthcare professionals and patients.&lt;/p&gt;
&lt;p&gt;The agency added that causal association is difficult to determine in postmarket reports, but that alternative causes of the hypertension were ruled out in well-documented cases.&lt;/p&gt;
&lt;p&gt;Healthcare professionals who determine didanosine is effective in treating a patient should monitor that patient for the development of portal hypertension and esophageal varices, the agency said.&lt;/p&gt;
&lt;p&gt;Didanosine is used in combination with other HIV medications to help maintain CD4 cells in patients.&lt;/p&gt;
&lt;p&gt;The drug already has a black box warning for lactic acidosis and hepatomegaly with steatosis.&lt;/p&gt;
&lt;p&gt;Like the antiretroviral agents hydroxyurea and ribavirin, didanosine has been associated with the development of liver toxicity.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_335"
                     title="Ultrasound Helps Predict Liver Damage in NAFLD (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/Gastroenterology/GeneralHepatology/tb/18211?impressionId=1265764519771"
                     
      &lt;p&gt;An ultrasound technique called transient elastography can accurately detect liver damage in most patients with non-alcoholic fatty liver disease (NAFLD), a condition that often accompanies obesity and type 2 diabetes, a new study found.&lt;/p&gt;
&lt;p&gt;Transient elastography (TE) accurately measured levels of liver stiffness, an indication of the amount of fibrosis, in more than 97% of patients with a body mass index below 30 kg/m&lt;sup&gt;2&lt;/sup&gt; and in 75% of obese patients, according to a report in the February issue of &lt;em&gt;Hepatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;The adoption of transient elastography could potentially spare two-thirds of NAFLD patients from liver biopsies,&quot; Victor de L&amp;#233;dinghen, MD, PhD, of H&amp;#244;pital Haut-L&amp;#233;v&amp;#234;que, in Pessac Cedex, France, and colleagues wrote. &quot;Since the prevalence of NAFLD is high in many affluent countries, this approach would be cost saving.&quot;&lt;/p&gt;
&lt;p&gt;Non-alcoholic fatty liver disease has become more common as the incidence of metabolic syndrome and obesity has grown. The condition can progress to cirrhosis and hepatocellular carcinoma, particularly among patients with non-alcoholic steatohepatitis (NASH), in which fat in the liver causes inflammation and tissue damage.&lt;/p&gt;
&lt;p&gt;Liver biopsy is typically used to determine levels of inflammation and fibrosis associated with NASH, but the procedure carries a small risk of hemorrhage, puncture of other internal organs, infection, and spread of cancer cells. Transvenous liver biopsy carries an additional risk of adverse reaction to the contrast material.&lt;/p&gt;
&lt;p&gt;These problems, in addition to the mixed results due to sampling variance&lt;strong&gt; &lt;/strong&gt;biopsies sometimes deliver, have researchers searching for alternative methods of determining the extent of liver fibrosis.&lt;/p&gt;
&lt;p&gt;L&amp;#233;dinghen and colleagues compared the accuracy of TE to biochemical tests for the diagnosis of fibrosis and cirrhosis in 246 NAFLD patients who underwent liver biopsies between May 2003 and April 2009 at University Hospital of Pessac and Prince of Wales Hospital in Hong Kong. The accuracy of the TE measurements was validated by biopsy results.&lt;/p&gt;
&lt;p&gt;Of the patients, 31 (12.6%) had advanced fibrosis and 25 (10.2%) had cirrhosis.&lt;/p&gt;
&lt;p&gt;The liver stiffness measurements of patients with F0, F1, F2, F3, and F4 stages of fibrosis were 5.7, 6.8, 7.8, 11.8, and 25.1 kPa, respectively (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001, by analysis of variance).&lt;/p&gt;
&lt;p&gt;TE was accurate for predicting fibrosis in patients with liver stiffness of at least 7.9 kPa; measurement and accuracy were not affected by hepatic steatosis, necroinflammation, and obesity.&lt;/p&gt;
&lt;p&gt;The most disagreement between the results of the TE and biopsy methods occurred in patients with short liver biopsy lengths and mild or no fibrosis.&lt;/p&gt;
&lt;p&gt;In patients with complete biochemical data, the accuracy of TE was compared with that of other means of predicting liver stiffness, and was found to be more reliable than aspartate aminotransferase&amp;#8211;to&amp;#8211;alanine aminotransferase ratio, aspartate aminotransferase&amp;#8211;to&amp;#8211;platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores.&lt;/p&gt;
&lt;p&gt;The authors cautioned that the results of the liver biopsies potentially could have been influenced by sampling bias and that referral&lt;strong&gt; &lt;/strong&gt;patients enrolled in the study may have had more advanced liver disease than the general population. They also noted that a significant proportion of obese patients were not analyzed because a liver stiffness measurement could not be obtained.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Leon Adams, PhD, of the University of Western Australia, noted that the majority of individuals with NAFLD will not develop liver-related morbidity or die from liver disease.&lt;/p&gt;
&lt;p&gt;&quot;Thus, he wrote, &quot;the difficulty facing the managing physician is predicting which patients are at greatest risk of developing cirrhosis, thus identifying those who will benefit most from specific treatments, more intensive therapy, and monitoring.&quot;&lt;/p&gt;
&lt;p&gt;The new study, he wrote, suggests that TE is effective at excluding advanced fibrosis and cirrhosis in patients with NAFLD. However, he argues that the technique requires further validation in obese and morbidly obese populations and that sensitivity of the test is likely to vary between differing patient populations, different medical personnel administering the test, and underlying prior probability of fibrosis.&lt;/p&gt;
&lt;p&gt;&quot;Lastly,&quot; he concluded, &quot;if noninvasive markers are going to form part of the routine assessment of the millions of individuals with NAFLD, the expense and availability of each modality may play a decisive role in which the noninvasive method is most appropriately taken up by community physicians and specialty hepatologists.&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;The study was supported by the Chinese University of Hong Kong.&lt;/p&gt;&lt;p&gt;Co-investigator Henry Lik-Yuen Chan reported receiving advising and speaking fees from Novartis, Bristol-Myers Squibb, Pharmasset, and Schering-Plough.&lt;/p&gt;&lt;p&gt;Co-investigator Sung reported receiving advising and speaking fees from AstraZeneca, GlaxoSmithKline, and Roche.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <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=1265764519771"
                     
      &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=1265764519771"
                     
      &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_1_517"
                     title="AASLD: Livers Donated After Cardiac Death Could Increase Transplant Supply"
                     score="-0.005"
                     href="